In vivo visualization of blood vessels in mouse ear by photoacoustic microscopy with transmissive liquid-crystal adaptive optics

Author(s):  
Yusuke Notsuka ◽  
Makoto Kurihara ◽  
Nobuyuki Hashimoto ◽  
Eiji Takahashi ◽  
Yoshihisa Yamaoka
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 ◽  
...  

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.


Author(s):  
Xiufeng Li ◽  
Victor T C Tsang ◽  
Lei Kang ◽  
Yan Zhang ◽  
Terence T W Wong

AbstractLaser diodes (LDs) have been considered as cost-effective and compact excitation sources to overcome the requirement of costly and bulky pulsed laser sources that are commonly used in photoacoustic microscopy (PAM). However, the spatial resolution and/or imaging speed of previously reported LD-based PAM systems have not been optimized simultaneously. In this paper, we developed a high-speed and high-resolution LD-based PAM system using a continuous wave LD, operating at a pulsed mode, with a repetition rate of 30 kHz, as an excitation source. A hybrid scanning mechanism that synchronizes a one-dimensional galvanometer mirror and a two-dimensional motorized stage is applied to achieve a fast imaging capability without signal averaging due to the high signal-to-noise ratio. By optimizing the optical system, a high lateral resolution of 4.8 μm has been achieved. In vivo microvasculature imaging of a mouse ear has been demonstrated to show the high performance of our LD-based PAM system.


Author(s):  
Yoshinori Harada ◽  
Eiji Takahashi ◽  
Yoshihisa Yamaoka ◽  
Yusuke Notsuka ◽  
Makoto Kurihara ◽  
...  

Sensors ◽  
2021 ◽  
Vol 21 (5) ◽  
pp. 1776
Author(s):  
Thi Thao Mai ◽  
Su Woong Yoo ◽  
Suhyun Park ◽  
Jin Young Kim ◽  
Kang-Ho Choi ◽  
...  

Vascular damage is one of the therapeutic mechanisms of photodynamic therapy (PDT). In particular, short-term PDT treatments can effectively destroy malignant lesions while minimizing damage to nonmalignant tissue. In this study, we investigate the feasibility of label-free quantitative photoacoustic microscopy (PAM) for monitoring the vasculature changes under the effect of PDT in mouse ear melanoma tumors. In particular, quantitative vasculature evaluation was conducted based on Hessian filter segmentation. Three-dimensional morphological PAM and depth-resolved images before and after PDT treatment were acquired. In addition, five quantitative vasculature parameters, including the PA signal, vessel diameter, vessel density, perfused vessel density, and vessel complexity, were analyzed to evaluate the influence of PDT on four different areas: Two melanoma tumors, and control and normal vessel areas. The quantitative and qualitative results successfully demonstrated the potential of the proposed PAM-based quantitative approach to evaluate the effectiveness of the PDT method.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3913-3913
Author(s):  
Britta Hardy ◽  
Annat Raiter ◽  
Chana Weiss ◽  
Alexander Battler

Abstract Angiogenesis is a fundamental process of generating new blood vessels by sprouting of endothelial cells from pre-existing vessels. Angiogenesis plays a crucial role in embryonic organ development and in adult vascular diseases. Adult tissues respond to hypoxia with compensatory mechanisms in which they can survive. Up-regulation of growth factors such as VEGF stimulate growth of vascular endothelial cells. Insufficient angiogenesis is relevant to many diseases such as coronary artery disease and delayed wound healing. Therapeutic angiogenesis aims to treat local hypovascularity by stimulating or inducing neovascularization for the treatment of ischemic vascular disease under the influence of an appropriate angiogenic molecule. We have identified a novel synthetic peptide, RoY, selected from a phage display peptide library by screening against endothelial cells under different physiological conditions. RoY peptide induces angiogenesis in vitro in a VEGF- independent mechanism and promotes collateral vessel growth and blood perfusion in vivo. In vitro assays demonstrated specific binding of peptide to endothelial cells and not to peripheral blood lymphocytes. Proliferation with RoY peptide at different dosages induces significant proliferation reaching 1.6 to 1.8-fold increase over control at 10ng/ml. The ability of RoY peptide to induce migration of endothelial cells was measured at different concentrations and under normoxic and hypoxic conditions using a Boyden cell migration chamber. RoY at 50 ng/ml induced a significant two-fold increase in migration compared to control and similar to VEGF. However, under hypoxia, RoY at 20 ng/ml induced a significant 2.5 fold increase in migration, significantly more migration than a similar dose under normoxia. RoY induced tube formation on Matrigel in both human umbilical vascular and dermal microvascular endothelial cells. A mouse ear angiogenesis model and a mouse ischemic hind limb model were used to evaluate the in vivo effects of RoY peptide. Angiogenesis in a mouse ear was induced by injection of RoY and was compared to the number of blood vessels in the control ear. RoY induced a 50% increase in the number of blood vessels in the treated ear. Ligation of the femoral artery in C57/ Bl mice induces ischemia in the operated leg. Injection of 1–10μg of RoY peptide to the operated ischemic legs resulted in a 100 percent perfusion in the operated leg versus the control non-operated leg. This increase was maintained and significant 21 days post operation while similar treatment with VEGF was maximal 14 days post operation and at 21 days the percent perfusion decreased. A possible angiogenic mechanisms of the synthetic novel peptide will be discussed. However, we have found that endothelial cells incubated with RoY peptide at different concentrations and times did not induce VEGF A secretion, nor was there an increase in VEGF receptors Flt-1 and Kdr, as revealed by FACS analysis. Gene expression of VEGF-A, Flt-1 and Kdr were not induced by RoY peptide, and the levels determined by Real Time PCR were not significantly different compared to controls. We have evaluated the angiogenic activity of a novel synthetic proangiogenic peptide. Characterization of the nature of endothelial cell signaling by this peptide will provide the basis for the development of targeted angiogenic therapy.


Circulation ◽  
1995 ◽  
Vol 92 (7) ◽  
pp. 1876-1882 ◽  
Author(s):  
Alexander Mülsch ◽  
Peter Mordvintcev ◽  
Eberhard Bassenge ◽  
Frank Jung ◽  
Bernd Clement ◽  
...  

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 192-198 ◽  
Author(s):  
Lorenzo Tarli ◽  
Enrica Balza ◽  
Francesca Viti ◽  
Laura Borsi ◽  
Patrizia Castellani ◽  
...  

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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