Trans-illuminated laser speckle imaging of collateral artery blood flow in ischemic mouse hindlimb

Joshua K Meisner,Jacqueline Niu,Suna Sumer,Richard J Price

doi:10.1117/1.jbo.18.9.096011

Joshua K Meisner, Jacqueline Niu + Show 2 more

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https://doi.org/10.1117/1.jbo.18.9.096011

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Abstract

The mouse ischemic hindlimb model is used widely for studying collateral artery growth (i.e., arteriogenesis) in response to increased shear stress. Nonetheless, precise measurements of regional shear stress changes along individual collateral arteries are lacking. Our goal is to develop and verify trans-illumination laser speckle flowmetry (LSF) for this purpose. Studies of defibrinated bovine blood flow through tubes embedded in tissue-mimicking phantoms indicate that trans-illumination LSF better maintains sensitivity with an increasing tissue depth when compared to epi-illumination, with an ∼50% reduction in the exponential decay of the speckle velocity signal. Applying trans-illuminated LSF to the gracilis muscle collateral artery network in vivo yields both improved sensitivity and reduced noise when compared to epi-illumination. Trans-illuminated LSF images reveal regional differences in collateral artery blood velocity after femoral artery ligation and are used to measure an ∼2-fold increase in the shear stress at the entrance regions to the muscle. We believe these represent the first direct measurements of regional shear stress changes in individual mouse collateral arteries. The ability to capture deeper vascular signals using a trans-illumination configuration for LSF may expand the current applications for LSF, which could have bearing on determining how shear stress magnitude and direction regulate arteriogenesis.

Highlights

The importance of adequate remodeling of pre-existing arterial interconnections to form endogenous collateral bypasses—i.e., arteriogenesis—is highlighted in the extensive link between adequate collateral development and enhanced patient outcomes with arterial occlusive disease.[1,2] The key initiating stimulus for arteriogenesis is increased shear stress.[3]
Epi-illumination laser speckle flowmetry (LSF) images exhibited significantly more noise when compared to the trans-illumination images [Fig. 4(b)], with much of this noise being generated by superficial fat cells overlying the muscle [Fig. 4(a), white arrows), especially in the collateral entry region near the saphenous artery
We report here the development and application of an adapted LSF method for measuring blood velocity in collateral arteries in response to femoral artery ligation (FAL) in the widely used mouse ischemic hindlimb model

Summary

Introduction

The importance of adequate remodeling of pre-existing arterial interconnections to form endogenous collateral bypasses—i.e., arteriogenesis—is highlighted in the extensive link between adequate collateral development and enhanced patient outcomes with arterial occlusive disease.[1,2] The key initiating stimulus for arteriogenesis is increased shear stress.[3] Upon occlusion of a major artery, downstream pressure is reduced, causing an increase in the pressure gradient, blood flow, and shear stress along pre-existing collateral arteries that bypass the occlusion Both the magnitude[4] and duration[5] of increased shear stress determine maximal collateral outgrowth and eventual resolution. These include cost and technical expertise, depth of imaging, and data integration over the observed vascular networks

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