scholarly journals Transcranial Imaging of Functional Cerebral Hemodynamic Changes in Single Blood Vessels using in vivo Photoacoustic Microscopy

2012 ◽  
Vol 32 (6) ◽  
pp. 938-951 ◽  
Author(s):  
Lun-De Liao ◽  
Chin-Teng Lin ◽  
Yen-Yu I Shih ◽  
Timothy Q Duong ◽  
Hsin-Yi Lai ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Cerebral Blood Volume ◽  
Hemoglobin Concentration ◽  
Photoacoustic Microscopy ◽  
Functional Changes ◽  
Sagittal Sinus ◽  
Microscopy Technique ◽  
Initial Dip ◽  
Transcranial Imaging

Optical imaging of changes in total hemoglobin concentration ( HbT), cerebral blood volume ( CBV), and hemoglobin oxygen saturation ( SO 2) provides a means to investigate brain hemodynamic regulation. However, high-resolution transcranial imaging remains challenging. In this study, we applied a novel functional photoacoustic microscopy technique to probe the responses of single cortical vessels to left forepaw electrical stimulation in mice with intact skulls. Functional changes in HbT, CBV, and SO 2 in the superior sagittal sinus and different-sized arterioles from the anterior cerebral artery system were bilaterally imaged with unambiguous 36 × 65- μm2 spatial resolution. In addition, an early decrease of SO 2 in single blood vessels during activation (i.e., ‘the initial dip’) was observed. Our results indicate that the initial dip occurred specifically in small arterioles of activated regions but not in large veins. This technique complements other existing imaging approaches for the investigation of the hemodynamic responses in single cerebral blood vessels.

scholarly journals Ultra-high-speed multi-parametric photoacoustic microscopy

2021 ◽  
Author(s):  
Song Hu ◽  
Fenghe Zhong
Keyword(s):  
High Speed ◽  
Laser Scanning ◽  
Ultrasonic Transducer ◽  
Hemoglobin Concentration ◽  
Blood Oxygenation ◽  
Flow Quantification ◽  
Photoacoustic Microscopy ◽  
Ultra High Speed ◽  
Working Distance

Multi-parametric photoacoustic microscopy (PAM) is uniquely capable of simultaneous, high-resolution mapping of blood hemoglobin concentration, oxygenation, and flow in vivo. However, its speed has been limited by the dense sampling required for blood flow quantification. To overcome this limitation, we have developed an ultra-high-speed multi-parametric PAM system, which enables simultaneous acquisition of ~500 densely sampled B-scans by superposing the rapid laser scanning across the line-shaped focus of a cylindrically focused ultrasonic transducer over the conventional mechanical scan of the optical-acoustic dual foci. A novel optical-acoustic combiner is designed and implemented to accommodate the short working distance of the transducer, enabling convenient confocal alignment of the dual foci in the reflection mode. This new system enables continuous monitoring of microvascular hemoglobin concentration, blood oxygenation, and flow over a 4.5 x 3 mm2 area in the awake mouse brain with high spatial and temporal resolution (6.9 μm and 0.3 Hz, respectively).

scholarly journals Retinoic acid upregulates β1-integrin in vascular smooth muscle cells and alters adhesion to fibronectin

2000 ◽  
Vol 279 (1) ◽  
pp. H382-H387 ◽  
Author(s):  
Meetha M. Medhora
Keyword(s):  
Smooth Muscle ◽  
Retinoic Acid ◽  
Vascular Smooth Muscle ◽  
Blood Vessels ◽  
Physiological Role ◽  
Cellular Growth ◽  
Integrin Subunit ◽  
Adult Rats ◽  
Functional Changes

Retinoic acid has an established physiological role in differentiation, development, and cellular growth. This study investigated the action of all- trans retinoic acid (ATRA) on vascular integrins, cell-surface receptors that control growth and remodeling of blood vessels. The β1-integrin subunit mRNA and protein was induced after treatment with ATRA in two different rat vascular smooth muscle cell lines. To relate this result to the in vivo state, the aortas from adult rats fed with therapeutic doses of ATRA were examined for β1-integrin protein. A significant upregulation of the integrin subunit was observed in vivo. To assess if this increase contributed to physiological changes in cellular function, cells treated with ATRA were tested for alterations in adhesion to extracellular matrix proteins. The cells exposed to the retinoid were seen to adhere more strongly to fibronectin, via the β1-integrin. These results showed that modulation of vascular integrins by ATRA in adult rats contributes to functional changes that can cause remodeling of blood vessels.

Vascular β-adrenoceptor function in hypertension and in ageing

2000 ◽  
Vol 78 (6) ◽  
pp. 433-452 ◽  
Author(s):  
Eva S Werstiuk ◽  
Robert MKW Lee
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Blood Vessels ◽  
Cellular Proliferation ◽  
Second Messengers ◽  
Cell Mass ◽  
Guanine Nucleotide Binding Protein ◽  
Receptor System ◽  
Functional Changes

Functional β-adrenoceptors (β-AR) have been identified and characterized in blood vessels under in vivo conditions as well as in vascular smooth muscle cells (SMC) grown in culture. Agonist occupancy of β-AR activates adenylyl cyclase (AC) via the stimulatory guanine nucleotide-binding protein (Gs) and leads to elevations in intracellular adenosine 3',5'-cyclic monophosphate levels (cAMP). Increased cAMP activates the cAMP-dependent protein kinase (PKA), with subsequent phosphorylation of various target proteins. This β-AR pathway interacts with several other intracellular signalling pathways via cross-talk, so that activation by β-AR agonists may also modulate other second messengers and protein kinases. SMC β-AR play an important role in SMC function. In intact blood vessels they mediate SMC relaxation by various intracellular mechanisms, ultimately causing a decrease in intracellular Ca2+ levels. In cultured SMC, activation of the β-AR pathway results in inhibition of cellular proliferation, the development of SMC polyploidy, and SMC apoptosis. Blood vessels from hypertensive animals are characterized by an increase in SMC cell mass, a greater incidence of SMC polyploidy in the aorta, and an impairment in the β-agonist-mediated SMC relaxation. Some of these changes may result from an attenuation of β-AR function due to agonist-induced receptor desensitization caused by the uncoupling of receptors from the Gs-AC system. The phosphorylated β-AR may in turn trigger new signals and activate different intracellular pathways. However, the details of these mechanisms are still unresolved. Since functional β-AR play such a prominent and multi-faceted role in SMC function, it is important to understand how these diverse physiological effects are mediated by this receptor system, and how they contribute to the development of hypertension. With ageing, a decrease in β-AR-Gs-AC coupling is observed, and this is implicated in the reduced responsiveness of SMC. The similarities in SMC β-AR functional changes in hypertension and in ageing suggest that the underlying mechanisms are also analogous.Key words: smooth muscle, β-adrenoceptors, cyclic AMP, protein kinase A, cell proliferation, polyploidy, relaxation, apoptosis, hypertension, ageing.

Effects of rapid mannitol infusion on cerebral blood volume

1986 ◽  
Vol 64 (1) ◽  
pp. 104-113 ◽  
Author(s):  
Patrick Ravussin ◽  
David P. Archer ◽  
Jane L. Tyler ◽  
Ernst Meyer ◽  
Mounir Abou-Madi ◽  
...  
Keyword(s):  
Blood Volume ◽  
Cerebral Blood Volume ◽  
Human Subjects ◽  
Venous Pressure ◽  
Hemoglobin Concentration ◽  
Rapid Infusion ◽  
Total Blood ◽  
Content Type ◽  
Positron Emission

✓ Positron emission tomography was used to study the effect of a rapid infusion of mannitol on cerebral blood volume (CBV) in five dogs and in three human subjects. The ability of mannitol to reduce intracranial pressure (ICP) has always been attributed to its osmotic dehydrating effect. The effects of mannitol infusion include increased osmolality, total blood volume, central venous pressure (CVP), and cerebral blood flow, and decreased hematocrit, hemoglobin concentration, serum sodium level, and viscosity. Mannitol's ability to dilate the cerebral vasculature, either directly or indirectly, and thus to transiently increase ICP, is a subject of controversy. By in vivo labeling of red cells with carbon-11, the authors were able to demonstrate an early increase in CBV in dogs of 20%, 27%, and 23% (mean increase, p < 0.05) at 1, 2, and 3 minutes, respectively, after an infusion of 20% mannitol (2 gm/kg over a 3-minute period). The animals' muscle blood volume increased by 27% (mean increase, p < 0.05) 2 minutes after infusion. In the human subjects, lower doses and a longer duration of infusion (1 gm/kg over 4 minutes) resulted in an increase in CBV of 8%, 14% (p < 0.05), and 10% at 1, 2, and 3 minutes, respectively, after infusion. In dogs, ICP increased by 4 mm Hg (mean increase, p < 0.05) 1 minute after the infusion, before decreasing sharply. The ICP was not measured in the human subjects. Hematocrit, hemoglobin, sodium, potassium, osmolality, heart rate, mean arterial pressure (MAP), and CVP were measured serially. Results of these measurements, as well as the significant decrease in MAP that occurred after mannitol infusion, are discussed. This study demonstrated that rapid mannitol infusion increases CBV and ICP. The increase in muscle blood volume, in the presence of a decreased MAP and an adequate CVP, suggests that mannitol may have caused vasodilation in these experiments.

Quantification of concentration changes in neonatal human cerebral oxidized cytochrome oxidase

1991 ◽  
Vol 71 (5) ◽  
pp. 1907-1913 ◽  
Author(s):  
A. D. Edwards ◽  
G. C. Brown ◽  
M. Cope ◽  
J. S. Wyatt ◽  
D. C. McCormick ◽  
...  
Keyword(s):  
Cytochrome Oxidase ◽  
Near Infrared ◽  
Cerebral Blood Volume ◽  
Arterial Oxygen Saturation ◽  
Hemoglobin Concentration ◽  
Carbon Dioxide Tension ◽  
Arterial Oxygen ◽  
Neonatal Brain ◽  
Concentration Changes

The oxygenation of cerebral cytochrome oxidase in vivo was investigated in eight newborn preterm infants. Near-infrared spectroscopy was used to quantify changes in the concentration of oxidized cytochrome oxidase ([CytO2]) observed during alterations in arterial oxygen saturation (SaO2) in the range of 85–99% and of carbon dioxide tension (PaCO2) in the range of 4.3–9.6 kPa. No relation was found between changes in SaO2 and [CytO2]. Alterations in PaCO2 were positively related both to changes in [CytO2] and total cerebral hemoglobin concentration [( Hb]t). The changes in [CytO2] ranged from 0.09 to 0.33 (median 0.21) mumol.l-1.kPa-1. The ratio [CytO2]/[Hb]t ranged from 0.06 to 0.12 (median 0.08). The relation of delta [CytO2] to the change in cerebral blood volume (delta CBV) was calculated: delta [CytO2]/delta CBV ranged from 0.09 to 0.18 (median 0.11) mumol/ml. These results define a fraction of cerebral cytochrome oxidase in the newborn infant that is oxidized after an increase in PaCO2 but demonstrate that a change in SaO2 in the range studied was not sufficient by itself to change [CytO2]. They differ from results of studies in adults; this may reflect significant differences between adult and neonatal brain.

In Vivo Spin Trapping of Glyceryl Trinitrate–Derived Nitric Oxide in Rabbit Blood Vessels and Organs

Circulation ◽  
1995 ◽  
Vol 92 (7) ◽  
pp. 1876-1882 ◽  
Author(s):  
Alexander Mülsch ◽  
Peter Mordvintcev ◽  
Eberhard Bassenge ◽  
Frank Jung ◽  
Bernd Clement ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Blood Vessels ◽  
Spin Trapping ◽  
Rabbit Blood

A High-Affinity Human Antibody That Targets Tumoral Blood Vessels

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 192-198 ◽  
Author(s):  
Lorenzo Tarli ◽  
Enrica Balza ◽  
Francesca Viti ◽  
Laura Borsi ◽  
Patrizia Castellani ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Small Cell Lung Carcinoma ◽  
Antibody Fragment ◽  
Human Colon ◽  
Experimental Models ◽  
Human Antibody ◽  
Cell Lung Carcinoma ◽  
High Affinity ◽  
Biodistribution Studies

Angiogenesis is a characteristic feature of many aggressive tumors and of other relevant disorders. Molecules capable of specifically binding to new-forming blood vessels, but not to mature vessels, could be used as selective vehicles and would, therefore, open diagnostic and therapeutic opportunities. We have studied the distribution of the ED-B oncofetal domain of fibronectin, a marker of angiogenesis, in four different tumor animal models: the F9 murine teratocarcinoma, SKMEL-28 human melanoma, N592 human small cell lung carcinoma, and C51 human colon carcinoma. In all of these experimental models we observed accumulation of the fibronectin isoform containing the ED-B domain around neovascular structures when the tumors were in the exponentially growing phase, but not in the slow-growing phase. Then we performed biodistribution studies in mice bearing a subcutaneously implanted F9 murine teratocarcinoma, using a high-affinity human antibody fragment (L19) directed against the ED-B domain of fibronectin. Radiolabeled L19, but not an irrelevant anti-lysozyme antibody fragment (D1.3), efficiently localizes in the tumoral vessels. The maximal dose of L19 accumulated in the tumor was observed 3 hours after injection (8.2% injected dose per gram). By virtue of the rapid clearance of the antibody fragment from the circulation, tumor-to-blood ratios of 1.9, 3.7, and 11.8 were obtained at 3, 5, and 24 hours, respectively. The tumor-targeting performance of L19 was not dose-dependent in the 0.7 to 10 μg range of injected antibody. The integral of the radioactivity localized in tumoral vessels over 24 hours was greater than 70-fold higher than the integral of the radioactivity in blood over the same time period, normalized per gram of tissue or fluid. These findings quantitatively show that new-forming blood vessels can selectively be targeted in vivo using specific antibodies, and suggest that L19 may be of clinical utility for the immunoscintigraphic detection of angiogenesis in patients.

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