Microvessel density estimation in the human brain by means of dynamic contrast‐enhanced echo‐planar imaging

Abstract

Animal studies have shown that in vivo estimates of microvessel density in the brain may be obtained from an MRI-measurable index (Q) provided that a sufficiently high dose of an intravascular paramagnetic contrast agent is employed. Q is determined from the shifts in the transverse relaxation rates induced by the contrast agent, and a high dose is required for the validity of analytic expressions relating Q to the microvessel density. However, the steady-state imaging techniques used in these prior investigations are not appropriate for humans, as the required contrast agent dose is too large. Here results of a pilot study with three subjects are reported. The results suggest that reliable Q measurements can be performed in the human brain at 1.5 T by using an interleaved spin-echo ( The microvessel density (MVD) is a useful prognostic indicator in many tumors (1,2), and is also of interest in the study of ischemia and aging (3-5). It was recently proposed that an MRI-measurable index (referred to as Q) may allow for in vivo quantitative estimates of the MVD (6,7). In particular, a good correspondence between MVD estimates based on Q and histologic values in the mouse brain was demonstrated in a study using superparamagnetic iron oxide particles (7).However, in order to obtain useful MVD values from Q measurements, a high dose of an intravascular paramagnetic or superparamagnetic contrast agent is required. Indeed, for a steady-state experiment, it has been argued that the necessary dose of gadopentetate dimeglumine (Gd-DTPA) at a field level of 1.5 T should be much greater than the standard clinical dose of 0.1 mmol/kg (6). In this article we show that one can overcome this limitation by measuring Q during the first passage of a contrast agent bolus, which makes Q-based MVD estimation feasible for clinical studies.In addition to the need for a high dose, a limitation of the previously proposed method is that it yields, within the model assumptions, a lower bound for the MVD. In regions where the distribution of vessel radii is narrow, this lower bound is expected to be a good MVD predictor (6,7). However, the presence of larger venules and arterioles can broaden the vessel distribution to the extent that the MVD will be significantly underestimated. For this reason, we introduce here a second Q-based quantity that is formally an MVD upper bound. Indeed, our results suggest that this upper bound actually provides a better estimator of the MVD than does the lower bound.Our method utilizes an interleaved spin-echo (SE)/gradient-echo (GE) echo-planar imaging (EPI) sequence and a bolus injection of triple the standard dose of Gd-DTPA administered at a rate of 5 ml/s, in order to achieve a high first-pass contrast agent concentration. Since triple-dose Gd-DTPA injections are safe and well tolerated (8), the method is suitable for human subjects. The Q-values are measured at the concentration peak during the first passage of the bolus through the brain's microvascular network, to ensure sufficient contrast-agent conc...

Vessel Size Imaging Reveals Pathological Changes of Microvessel Density and Size in Acute Ischemia

“…One study has published a quantitative Q assessment in human brain tissue (Jensen et al, 2006). The Q values in our study are somewhat lower than those found by Jensen et al, in which a triple dose of contrast agent has been administered and only the maximum signal drop points are used to estimate Q.…”

“…In the mouse brain, k has been proposed as 329 s/mm 2 by Wu et al (2004), yet it is not available for the human brain. Jensen et al (2006) showed a possible way to calculate the lower and upper bounds of MVD in vivo by using Q. However, the lower and upper boundaries, which differ by two orders of magnitude, do not allow an accurate estimate of MVD.…”

Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis

“…Analysis then showed that a scaled ratio, vessel density (Q) : DR 2 /(DR 2 *) 2/3 , correlated to histologic estimates of areal Q; this parameter has the advantage of being independent of the concentration of contrast agent present in the blood (18,19). Further development of this work resulted in a theoretical expression for vessel size index (VSI) (a weighted mean radius of all vessels contained within a voxel) that included the effects of diffusion and Dx, the susceptibility difference between blood and tissue due to the USPIO contrast agent (20).…”

Intravoxel partially coherent motion technique: Characterization of the anisotropy of skeletal muscle microvasculature

“…Although they lack the spatial and temporal resolution of optical methods, MRI methods can retrieve indirect information about the microcirculatory bed by using either magnetic susceptibility effects or blood displacement effects. Magnetic susceptibility effects can be used to probe the architecture of the microvasculature (9), whereas measuring the effects of blood displacement locally can be used to quantify perfusion (10) or directional blood transport (11). Techniques that measure perfusion rely on quantifying the terminal blood deposition, whereas techniques that measure blood transport rely on measuring certain parameters of the blood velocity distribution.…”