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Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue.

Sakadžić S, Mandeville ET, Gagnon L, Musacchia JJ, Yaseen MA, Yucel MA, Lefebvre J, Lesage F, Dale AM, Eikermann-Haerter K, Ayata C, Srinivasan VJ, Lo EH, Devor A, Boas DA - Nat Commun (2014)

Bottom Line: Here we show that parenchymal arterioles are responsible for 50% of the extracted O2 at baseline activity, and the majority of the remaining O2 exchange takes place within the first few capillary branches.Our results challenge the common perception that capillaries are the major site of O2 delivery to cerebral tissue.The understanding of oxygenation distribution along arterio-capillary paths may have profound implications for the interpretation of blood-oxygen-level dependent (BOLD) contrast in functional magnetic resonance imaging and for evaluating microvascular O2 delivery capacity to support cerebral tissue in disease.

View Article: PubMed Central - PubMed

Affiliation: Optics Division, MHG/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.

ABSTRACT
What is the organization of cerebral microvascular oxygenation and morphology that allows adequate tissue oxygenation at different activity levels? We address this question in the mouse cerebral cortex using microscopic imaging of intravascular O2 partial pressure and blood flow combined with numerical modelling. Here we show that parenchymal arterioles are responsible for 50% of the extracted O2 at baseline activity, and the majority of the remaining O2 exchange takes place within the first few capillary branches. Most capillaries release little O2 at baseline acting as an O2 reserve that is recruited during increased neuronal activity or decreased blood flow. Our results challenge the common perception that capillaries are the major site of O2 delivery to cerebral tissue. The understanding of oxygenation distribution along arterio-capillary paths may have profound implications for the interpretation of blood-oxygen-level dependent (BOLD) contrast in functional magnetic resonance imaging and for evaluating microvascular O2 delivery capacity to support cerebral tissue in disease.

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PO2 distribution measured inside the penetrating arterioles duringnormocapnia(a) Maximum intensity projection of the microvascular structure obtained byTPM showing diving arteriole at the center (red arrow). Scale bar, 50 μm.(b) PO2 map inside the penetrating arteriole in a,100 μm below the cortical surface. Scale bar, 20 μm. Insert in the upperleft hand side of the panel b shows a two-dimensional image from amicrovascular stack (a) at the PO2 imaging depth (100 μmbelow the cortical surface). (c) Radial intra-arteriolar PO2profiles (radial distance calculated from the vessel axis (vessel center) to the vesselwall) from 4 penetrating arterioles similar to the example vessel presented ina and b. For each PO2 profile, a star indicates thesmallest radius where the mean PO2 is significantly lower than thePO2 at the vessel center (two-sample t-test; P <=0.034). Data are expressed as mean ± s.e.m., calculated as detailed in the methods.Results are presented for n = 3 mice.
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Figure 2: PO2 distribution measured inside the penetrating arterioles duringnormocapnia(a) Maximum intensity projection of the microvascular structure obtained byTPM showing diving arteriole at the center (red arrow). Scale bar, 50 μm.(b) PO2 map inside the penetrating arteriole in a,100 μm below the cortical surface. Scale bar, 20 μm. Insert in the upperleft hand side of the panel b shows a two-dimensional image from amicrovascular stack (a) at the PO2 imaging depth (100 μmbelow the cortical surface). (c) Radial intra-arteriolar PO2profiles (radial distance calculated from the vessel axis (vessel center) to the vesselwall) from 4 penetrating arterioles similar to the example vessel presented ina and b. For each PO2 profile, a star indicates thesmallest radius where the mean PO2 is significantly lower than thePO2 at the vessel center (two-sample t-test; P <=0.034). Data are expressed as mean ± s.e.m., calculated as detailed in the methods.Results are presented for n = 3 mice.

Mentions: Our measurements provided two types of evidence that oxygen is readily extractedfrom the cortical arterioles at baseline conditions: 1) Dense cross-sectionalPO2 maps inside the diving cortical arterioles during normocapnia revealedpronounced PO2 gradients from the vessel centers to the vessel walls (Fig. 2), indicating oxygen supply to the tissue from thearterioles (for simulation results supporting this observation please see Supplementary Fig. 2). This isconsistent with previously documented significant tissue PO2gradients3,16,18 and a marked absence ofcapillaries in the vicinity of penetrating arterioles.21 2) Our measurements along diving arterioles and their branches showedthat oxygenation rapidly decreased as blood moved downstream along the arteriolar tree(Fig. 3). PO2 in normocapnia startedfrom above 100 mmHg (SO2 ≈ 0.95) in larger pial arterioles with diameter≥40 μm and decayed to ≈65 mmHg (SO2 ≈ 0.73) in thesmallest arterioles with diameters below 10 μm, with a decay rate that increasedrapidly with decreasing vessel diameter. The mean PO2 from all precapillaryarterioles – arteriolar segments immediately proximal to the capillaries –was 66 mmHg (SO2 = 0.78), indicating ΔSO2 = 0.17 from thearteriolar segments during normocapnia. This represents 50% of the SO2difference between large pial arterioles and venules with diameters ≥40 μm(ΔSO2,A-V = 0.33). A similar observation can be made by examining thePO2 and SO2 variation with microvascular segment branching orderand distance along the microvascular paths with respect to the pial vessels (Supplementary Fig. 3).


Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue.

Sakadžić S, Mandeville ET, Gagnon L, Musacchia JJ, Yaseen MA, Yucel MA, Lefebvre J, Lesage F, Dale AM, Eikermann-Haerter K, Ayata C, Srinivasan VJ, Lo EH, Devor A, Boas DA - Nat Commun (2014)

PO2 distribution measured inside the penetrating arterioles duringnormocapnia(a) Maximum intensity projection of the microvascular structure obtained byTPM showing diving arteriole at the center (red arrow). Scale bar, 50 μm.(b) PO2 map inside the penetrating arteriole in a,100 μm below the cortical surface. Scale bar, 20 μm. Insert in the upperleft hand side of the panel b shows a two-dimensional image from amicrovascular stack (a) at the PO2 imaging depth (100 μmbelow the cortical surface). (c) Radial intra-arteriolar PO2profiles (radial distance calculated from the vessel axis (vessel center) to the vesselwall) from 4 penetrating arterioles similar to the example vessel presented ina and b. For each PO2 profile, a star indicates thesmallest radius where the mean PO2 is significantly lower than thePO2 at the vessel center (two-sample t-test; P <=0.034). Data are expressed as mean ± s.e.m., calculated as detailed in the methods.Results are presented for n = 3 mice.
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Related In: Results  -  Collection

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Figure 2: PO2 distribution measured inside the penetrating arterioles duringnormocapnia(a) Maximum intensity projection of the microvascular structure obtained byTPM showing diving arteriole at the center (red arrow). Scale bar, 50 μm.(b) PO2 map inside the penetrating arteriole in a,100 μm below the cortical surface. Scale bar, 20 μm. Insert in the upperleft hand side of the panel b shows a two-dimensional image from amicrovascular stack (a) at the PO2 imaging depth (100 μmbelow the cortical surface). (c) Radial intra-arteriolar PO2profiles (radial distance calculated from the vessel axis (vessel center) to the vesselwall) from 4 penetrating arterioles similar to the example vessel presented ina and b. For each PO2 profile, a star indicates thesmallest radius where the mean PO2 is significantly lower than thePO2 at the vessel center (two-sample t-test; P <=0.034). Data are expressed as mean ± s.e.m., calculated as detailed in the methods.Results are presented for n = 3 mice.
Mentions: Our measurements provided two types of evidence that oxygen is readily extractedfrom the cortical arterioles at baseline conditions: 1) Dense cross-sectionalPO2 maps inside the diving cortical arterioles during normocapnia revealedpronounced PO2 gradients from the vessel centers to the vessel walls (Fig. 2), indicating oxygen supply to the tissue from thearterioles (for simulation results supporting this observation please see Supplementary Fig. 2). This isconsistent with previously documented significant tissue PO2gradients3,16,18 and a marked absence ofcapillaries in the vicinity of penetrating arterioles.21 2) Our measurements along diving arterioles and their branches showedthat oxygenation rapidly decreased as blood moved downstream along the arteriolar tree(Fig. 3). PO2 in normocapnia startedfrom above 100 mmHg (SO2 ≈ 0.95) in larger pial arterioles with diameter≥40 μm and decayed to ≈65 mmHg (SO2 ≈ 0.73) in thesmallest arterioles with diameters below 10 μm, with a decay rate that increasedrapidly with decreasing vessel diameter. The mean PO2 from all precapillaryarterioles – arteriolar segments immediately proximal to the capillaries –was 66 mmHg (SO2 = 0.78), indicating ΔSO2 = 0.17 from thearteriolar segments during normocapnia. This represents 50% of the SO2difference between large pial arterioles and venules with diameters ≥40 μm(ΔSO2,A-V = 0.33). A similar observation can be made by examining thePO2 and SO2 variation with microvascular segment branching orderand distance along the microvascular paths with respect to the pial vessels (Supplementary Fig. 3).

Bottom Line: Here we show that parenchymal arterioles are responsible for 50% of the extracted O2 at baseline activity, and the majority of the remaining O2 exchange takes place within the first few capillary branches.Our results challenge the common perception that capillaries are the major site of O2 delivery to cerebral tissue.The understanding of oxygenation distribution along arterio-capillary paths may have profound implications for the interpretation of blood-oxygen-level dependent (BOLD) contrast in functional magnetic resonance imaging and for evaluating microvascular O2 delivery capacity to support cerebral tissue in disease.

View Article: PubMed Central - PubMed

Affiliation: Optics Division, MHG/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.

ABSTRACT
What is the organization of cerebral microvascular oxygenation and morphology that allows adequate tissue oxygenation at different activity levels? We address this question in the mouse cerebral cortex using microscopic imaging of intravascular O2 partial pressure and blood flow combined with numerical modelling. Here we show that parenchymal arterioles are responsible for 50% of the extracted O2 at baseline activity, and the majority of the remaining O2 exchange takes place within the first few capillary branches. Most capillaries release little O2 at baseline acting as an O2 reserve that is recruited during increased neuronal activity or decreased blood flow. Our results challenge the common perception that capillaries are the major site of O2 delivery to cerebral tissue. The understanding of oxygenation distribution along arterio-capillary paths may have profound implications for the interpretation of blood-oxygen-level dependent (BOLD) contrast in functional magnetic resonance imaging and for evaluating microvascular O2 delivery capacity to support cerebral tissue in disease.

Show MeSH
Related in: MedlinePlus