Time‐of‐flight quantitative measurements of blood flow in mouse hindlimbs

Wagner, Shawn; Helisch, Armin; Bachmann, Georg; Schäper, Wolfgang

doi:10.1002/jmri.20025

Cited by 26 publications

(26 citation statements)

References 36 publications

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“…Then 1-mL samples were run through the flow phantom at varying linear flow speeds between 600 μm∕s and 15 cm∕s. The latter value reflects a higher flow speed than we anticipate in limb blood vessels in mice in vivo, 22,25,26 and the former is the lowest flow speed that the microsyringe pump could produce. Experiments were repeated three times for each flow speed.…”

Section: Characterization Of the Useful Dffc Flow Speed Rangementioning

confidence: 99%

“…The highest flow speed (15 cm∕s) represents a faster speed than occurs normally in blood vessels in mice in vivo. 22,25,26 The slowest flow speed used here (600 μm∕s) was the lower limit that could be produced with our microsyringe pump rather than a detection limit of our instrument. We note that the relatively large standard deviations for each point shown do not reflect error in the measurements, but real observed variations in flow speeds of the microspheres across the flow profile as discussed above.…”

Section: Analysis Of Dffc Flow Speed Rangementioning

confidence: 99%

“…Our strategy was to develop a fluorescence sensing ring that would be placed around a relatively narrow, 2 to 3 mm limb of a mouse, where total circulating blood flow rates are approximately 0.2 to 0.5 mL per minute. 22 Therefore, in principle, the entire ∼2.5 mL blood volume of a mouse could be interrogated in minutes. As we discuss, the principal engineering challenges in developing this instrument were i. high-sensitivity detection of very low signal levels from individual cells, ii.…”

Section: Introductionmentioning

confidence: 99%

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Instrument for fluorescence sensing of circulating cells with diffuse light in mice in vivo

Zettergren¹,

Vickers²,

Runnels

et al. 2012

J. Biomed. Opt.

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Section: Characterization Of the Useful Dffc Flow Speed Rangementioning

confidence: 99%

Section: Analysis Of Dffc Flow Speed Rangementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Instrument for fluorescence sensing of circulating cells with diffuse light in mice in vivo

Zettergren¹,

Vickers²,

Runnels

et al. 2012

J. Biomed. Opt.

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“…The arterial segment between the ligatures was excised ( Figure 1A). Treated mice received 1ϫ10 9 pfu of Ad-PR39 or Ad-Null at the time of surgery by 2 injections (15 L each), placed 2 to 3 mm deep, 1 in the adductor and 1 in the quadriceps muscle at the level of femoral artery ligation.…”

Section: Hindlimb Ischemia Modelmentioning

confidence: 99%

“…Measurements were based on a modification of a TOF method used previously. 9 The image acquisition was performed with the mice under anesthesia with 1.5% isoflurane in oxygen at 37°C. A gradient echo MR sequence was used with TR/TE/␣ϭ 0.03/0.0035/90°, slice thickness 600 m, 3ϫ3-cm field of view, and 512ϫ128 matrix size, resulting in a pixel resolution of 59ϫ234ϫ600 m. For processing, a region of interest was selected in an area of the nonischemic leg that did not include any visible vessels.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

Delayed Arteriogenesis in Hypercholesterolemic Mice

et al. 2005

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Background— Hypercholesterolemia has been reported to inhibit ischemia-induced angiogenesis. To address its effects on arteriogenesis, we investigated arterial growth in hypercholesterolemic low-density lipoprotein receptor −/− /ApoB-48 −/− (HCE) mice. Methods and Results— The extent and the time course of arteriogenesis after femoral artery ligation was evaluated in HCE and strain-matched control mice. Distal limb perfusion was measured by laser Doppler imaging, whereas MRI was used to visualize arterial flow and micro-computed tomography to assess vascular growth. After femoral artery ligation, serial laser Doppler imaging demonstrated significantly delayed restoration of perfusion in untreated HCE compared with control mice (day 3, 0.09 versus 0.19, P <0.05). Treatment with Ad-PR39 in control mice led to a significant restoration of arterial blood flow and tissue perfusion at day 3, whereas in HCE mice, hindlimb perfusion began increasing only by day 7. Micro-CT analysis confirmed increased growth of smaller arterioles (16 to 63 μm in diameter) in the Ad-PR39–treated control compared with HCE mice. The delay in arteriogenesis in HCE mice correlated with delayed tissue appearance of F4/80 + cells. Analysis of gene expression after Ad-PR39 treatment demonstrated that HCE mice had significantly reduced expression of FGF receptor 1, hypoxia-inducible factor-1α, vascular cell adhesion molecule-1, macrophage scavenger receptor-1, and cyclophilin A compared with controls 3 days after arterial ligation that equalized by day 7, mimicking relative changes in arteriogenesis and tissue perfusion. Conclusions— Hypercholesterolemia results in delayed native arteriogenesis because of reduced early monocyte/macrophage influx and delayed and impaired arterial growth response to growth factor therapy.

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Dynamic changes in murine vessel geometry assessed by high‐resolution magnetic resonance angiography: A 9.4T study

Jacoby

Böring

Beck

et al. 2008

Magnetic Resonance Imaging

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Purpose:To establish high-resolution magnetic resonance angiography (MRA) protocols to monitor and quantify dynamic changes of vascular remodeling in pathologic mouse models. Materials and Methods:Time-of-flight (TOF) MRA of murine vessels was performed at 9.4T to monitor temporal alterations in the vessel structure in two frequently used injury models (wire denudation of carotid artery and femoral artery occlusion). Quantification of vessel morphology was performed with the use of in-house-developed software and validated by estimation of inter-and intraobserver variabilities and reproducibility, and by correlation with histological data. Results:MRA-based volume determination exhibited low intra-and interobserver variabilities and high reproducibility. Furthermore, good correlations with histological data were found four weeks after injury (R 2 ϭ 0.970). Two highresolution image series are presented to demonstrate the applicability of the technique: 1) the time course of a vessel stenosis that reopens by thrombus recanalization, and 2) the continuous restoration of blood flow by collateral vessel formation during arteriogenesis after induction of hindlimb ischemia. Conclusion:We describe high-resolution MRA imaging protocols that are suitable for sensitively measuring the extent and time course of changes in vessel morphology in mice in a repetitive manner without any contrast agent. This methodology provides a reliable tool for noninvasive monitoring of vascular lesion development or neovascularization in transgenic mice. GENETICALLY MODIFIED MICE HAVE BEEN well established as models for studying dynamic processes in vascular biology, such as the development of vessel stenosis or the initiation of neovascularization. For this purpose, generated mutants are frequently subjected to experimental models, such as wire-induced denudation of the common carotid artery (CCA) (1,2) and ligation of the femoral artery (hindlimb ischemia) (3,4), respectively. In general, these models are evaluated by ex vivo histopathology, which provides information at the time of harvest only. Furthermore, this technique is partially tissue-destructive, only a limited region of the vessel is accessible to histology, and the analysis of luminal area and stenosis is complicated by fixation artifacts. Consequently, noninvasive, repetitive three-dimensional monitoring would be highly desirable for continuous, quantitative vessel analysis.All previous MR-based approaches to study the formation of collateral vessels after hindlimb ischemia were, to our knowledge, restricted to a qualitative threedimensional assessment of newly developed flow (5,6) or to quantitative analysis of two-dimensional gradient echo images (6 -9). Similarly, a two-dimensional MRI method was used to monitor alterations in vessel morphology after wire denudation of the CCA by Manka et al (10). However, the reported method requires relatively long sampling times (about 40 minutes) as well as complex analysis procedures. Nevertheless, the MR data could be satisfactorily c...

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Time‐of‐flight quantitative measurements of blood flow in mouse hindlimbs

Cited by 26 publications

References 36 publications

Instrument for fluorescence sensing of circulating cells with diffuse light in mice in vivo

Instrument for fluorescence sensing of circulating cells with diffuse light in mice in vivo

Delayed Arteriogenesis in Hypercholesterolemic Mice

Dynamic changes in murine vessel geometry assessed by high‐resolution magnetic resonance angiography: A 9.4T study

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