Automated multiscale vessel analysis for the quantification of MR angiography of peripheral arteriogenesis

Abstract

Purpose: To automatically analyze the time course of collateralization in a rat hindlimb ischemia model based on signal intensity distribution (SID). Materials and Methods:Time-of-flight magnetic resonance angiograms (TOF-MRA) were acquired in eight rats at 2, 7, and 21 days after unilateral femoral artery ligation. Analysis was performed on maximum intensity projections filtered with multiscale vessel enhancement filter. Differences in SID between ligated limb and a reference region were monitored over time and compared to manual collateral artery identification.Results: The differences in SID correlated well with the number of collateral arteries found with manual quantification. The time courses of ultrasmall (diameter (0.5 mm) and small (diameter %0.5 mm) collateral artery development could be differentiated, revealing that maturation of the collaterals and enlargement of their feeding arteries occurred mainly after the first week postligation.Conclusion: SID analysis performed on axial maximum intensity projections is easy to implement, fast, and objective and provides more insight in the time course of arteriogenesis than manual identification. COLLATERAL ARTERIES developing from preexistent arterioles can act as natural bypasses in patients with peripheral or coronary arterial occlusive disease (1). Currently, therapies stimulating the formation of collateral arteries (ie, arteriogenesis) and restoring the impaired blood supply are explored (2-4). Accurate evaluation of such novel treatments strongly depends on image acquisition and analysis techniques that can detect and quantify the vascular responses both in experimental and clinical settings. Previously, noncontrast-enhanced inflow magnetic resonance angiography (MRA) techniques such as time-of-flight (TOF) MRA have been successfully used to noninvasively quantify collateralization in small animal ischemic hindlimb models (5-8).Collaterals are usually identified and quantified manually on (rotating) maximum intensity projections (MIPs) using the Longland definition (9), which requires identification of the collateral stem, mid-, and reentry zone. Visualization of complete trajectories is challenging due to inflow artifacts, flow voids for in-plane arteries (10), and the ultrasmall collateral artery calibers ((0.5 mm). Moreover, manual quantification is time-consuming, observer-dependent, and provides little information on changes in vessel size and physiological impact. A physiologically more relevant measure would be the blood volume or flow of the collateral arteries. Wagner et al (5) proposed a method to quantify collateral flow based on the dependence between pixel signal intensity and the amount and speed of inflow of unsaturated blood spins. The signal intensity histogram of TOF angiograms may provide surrogate parameters for changes in vessel morphology, as the signal intensity distribution depends on vessel size (11). A problem to overcome is the small volume fraction of arteries in hindlimbs compared to the large volume of background tissue. ...

Glyoxalase-1 overexpression partially prevents diabetes-induced impaired arteriogenesis in a rat hindlimb ligation model

“…Seven days post ligation the animals were imaged in supine position in a 7.0 Tesla MR system with a birdcage quadrature coil (Bruker Biospin, Ettlingen, Germany) as described earlier [ 9 ]. Briefly, the angiography protocol consisted of a multi-slice 2D flow-compensated gradient echo sequence.…”

“…The thickness and location of the slab was adjusted to obtain optimal depiction of the collaterals. In addition, quantification of the collateralization was assessed by signal intensity distribution analysis (for a detailed description, see [ 9 ]) The collateral index represents the normalized volume fraction of vessels with a diameter of approximately 0.5 mm and is therefore used as a measure for the volume of collateral arteries.…”

A modified rat model of hindlimb ischemia for augmentation and functional measurement of arteriogenesis

“…Collateral vessels themselves may be imaged conventionally through tissue sectioning and immunohistochemistry, whole-tissue imaging techniques such as arteriography or contrast-enhanced micro-computed tomography (micro-CT) or in vivo imaging technology such as optical coherence tomography-based microangiography [8-11]. Magnetic resonance imaging techniques have been used to quantitatively assess structure and flow of collateral networks in living animal models of peripheral arteriogenesis [12-14]. Even these sophisticated imaging methods have limitations accounting for numerous hemodynamic, anatomic and vasoactive variables that may obscure the true capacity of the developed collateral network.…”