Quantitative CBV measurement from static T₁ changes in tissue and correction for intravascular water exchange

Abstract

The steady-state (SS) approach has been proposed to measure quantitative cerebral blood volume (CBV). However, it is known that the CBV value in SS (CBV SS ) is subject to error resulting from the effects of water diffusion from the intra-to extravascular space. CBV SS measurements were simulated in both fastand no-water-exchange limits, and compared with measured CBV SS values to determine which limiting case is appropriate. Twenty-eight patients were scanned with a segmented LookLocker echo-planar imaging (LL-EPI) sequence before and after the injection of 0.1 mmol/kg of a T 1 -shortening contrast agent. Signal changes and T 1 values of brain parenchyma and the blood pool were measured pre-and postcontrast. These signal changes and T 1 values, in combination with the simulated results, were used to estimate water-exchange rates. We found that the intra-to extravascular water-exchange rates in white matter (WM) and gray matter (GM) were 0.9 and 1.6 s -1 , respectively. With these water-exchange rates, the fast-water-ex- In recent years MRI techniques have been developed to quantify a variety of physiologic parameters that reflect pathology. Parameters related to tissue perfusion have been shown to reflect underlying pathophysiology in a variety of diseases of the central nervous system, including ischemic stroke, tumor neovascularity, neoplasia, and Alzheimer's disease (1-5). Imaging techniques to measure relative cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) have been established (6). However, reliable quantification of these parameters has been elusive.When the blood-brain barrier (BBB) is intact, one can measure CBV values using contrast-enhanced MRI by comparing T 1 maps or T 1 -weighted images measured before and after the intravascular injection of a T 1 -shortening contrast agent (7,8). This approach is conventionally referred to as the steady-state CBV (CBV SS ) measurement. However, quantification of CBV SS has been problematic due to under-or overestimation resulting from the continual exchange of water from the intravascular space (9). The effect of water exchange has been extensively modeled (10), and there are predictable trends that depend on the approximations of the exchange rate. There are two limiting cases-the "fast-exchange" and "no-exchange" limits-that require different approaches to calculate CBV SS .We attempted to determine which limiting case of the exchange rate is valid in healthy tissue by performing direct measurements in humans. First we simulated CBV measurement in both fast-and no-water-exchange limits to determine the behavior in the range of values relevant to normal white matter (WM) and gray matter (GM). We then compared these simulated results with data acquired in patients. Then we used in vivo data to determine which limiting case is valid, and to determine the intravascular (to extravascular) and extravascular (to intravascular) water-exchange rates. Finally, with the optimum values for exchange rate determined, we developed a techni...

Absolute quantification of perfusion by dynamic susceptibility contrast MRI using Bookend and VASO steady-state CBV calibration: a comparison with pseudo-continuous ASL

“…In this study, the effect of the CA might have been even smaller than in previous studies since the estimated ΔR1 in blood in this study was 2.2 s -1 (at a CA dose of 0.12 mmol/kg), while earlier studies showed values about 2-4 times higher after injection of 0.1 mmol/kg of CA [7,16]. The reason for this is not fully understood, but one possible explanation is that, in our study, a longer time delay between the bolus passage and the post-CA images, acquired at steady-state, were used.…”

“…According to the Bookend concept, CBV can be obtained from T1 measurements before and after CA administration using the following equations [7,13]:…”

“…Eq. 3 assumes fast water exchange between the intra-and the extra-vascular space [14,15], and WCF(ΔR 1 ) corrects for expected deviations from the fast-water-exchange limit [7]. The WCF is dependent on the concentration of CA in blood as well as on sequence parameters in the T1 measurements and can be obtained by fitting a curve, of the form a·ΔR 1 2 +b·ΔR 1 +c to data plotted as a function of the change in longitudinal relaxation rate, ΔR1, in blood [7,16].…”

“…To avoid noise effects the selected pixels were also required to show high signal (i.e., being among the 3% of the voxels with the highest signal) at the last time point in the post-CA images from the Look-Locker sequence. CBV true,WM = 1.91 ml/100g and CBV true,GM = 3.85 ml/100g was used [7] for the estimation of WCF, and the fitting was carried out using a non-linear least square fitting (with zero as lower limit and infinity as upper limit).…”

“…In the previously proposed Bookend method [7,8], CBV is estimated using steady-state measurements of T1 before and after contrast agent (CA) administration to determine the CF. The Bookend method has previously been compared to positron emission tomography (PET), which is commonly regarded as the gold standard method for CBF measurements, and a good correlation between the two methods was observed [9].…”