The lecture targets physicists, engineers and physicians with an interest in advanced brain perfusion imaging with intravoxel incoherent motion.
The lecture targets physicists, engineers and physicians with an interest in advanced brain perfusion imaging with intravoxel incoherent motion.
Introduction
The thought that in-vivo intravoxel incoherent motion (IVIM) magnetic resonance signal is influenced by blood motion in the microvasculature suggests that local and quantitative perfusion information can be obtained in a simple and elegant way from a few diffusion-weighted images, without contrast injection. The perfusion effects on diffusion-weighted signal can be modeled by a bi-exponential signal equation model (11):
(1) \[\frac{S(b)}{S_0}=fe^{-bD^*}+(1-f)e^{-bD}\]
where f stands for the perfusion fraction, D the diffusion coefficient, D* the pseudo-diffusion coefficient, S the signal at given b-value, and S0 the signal at b=0. The b-value summarizes the effect of the diffusion-encoding gradient pulses on the signal, and depends on the shape, duration, and amplitude of the gradients. For example, for Stejskal-Tanner pulsed gradients (1), which consists of two short pulses of duration δ, amplitude G, and separated by a short amount of time Δ, the b-value is given by (2) \[b=\gamma^2G^2\delta^2(\triangle-\frac{\delta}{3})\]where γ is the proton gyromagnetic ratio.
Acquisition strategy and post-processing
IVIM perfusion imaging requires the acquisition of multiple b-value images, usually around 10 to 30, at b-values between 0 and 1000 s/mm2, to avoid non-Gaussian diffusion restriction effects that appear at larger b-value (2). Because blood volume in the brain is relatively low, around 3-4% of brain tissue (3), images should be acquired at optimized signal to noise ratio, and in particular, to reduce unnecessary signal loss due to relaxation effects, TE should be minimized. For each b-value, images are usually acquired with diffusion-encoding gradient pulses in 3 orthogonal directions (or more), from which the geometric mean of the signal is taken, because the latter is independent of the chosen directions (see p. 842 in (4)), which is particularly relevant in the highly anisotropic white matter: of the brain:
(3) \[S=\sqrt[3]{S_xS_yS_z} = \sqrt[3]{S_{Rx}S_{Ry}S_{Rz}}\]
with R⋲ S0(3), the rotation group.
The IVIM parameters are then estimated by fitting equation (1), most commonly in a two steps procedure using the Levenberg-Marquardt algorithm (5,6): In the first step, assuming D* >> D, only the second term in equation (1) is fitted for a b value greater than 200 s/mm2 (the threshold above which perfusion effects are assumed to be negligible) for the single parameter D. In the second step, equation (1) is fitted for f and D* for all the b values, while keeping D constant. Several alternatives to improve image quality have been proposed, such as Bayesian estimation approaches (7,8), fusion bootstrap moves (9), and total variation methods (10).
IVIM perfusion maps interpretations
The IVIM parameter f can be understood as the “incoherently flowing” cerebral blood volume. D*, the pseudo-diffusion coefficient, or in other words, “the apparent diffusion coefficient of the blood compartment”, holds information on cerebral blood speed. It has been suggested that the scalar multiplication of the f and the D* parameters, fD*, is related to cerebral blood flow (11). It is generally accepted that D* is more difficult to evaluate than f, in the sense that D* maps are more noisy, and therefore clinical applications of the IVIM perfusion method often concentrate on the f parameter. In the brain, an important confounding factor is the presence of cerebrospinal fluid, which surrounds the brain, in the so-called subarachnoid space, as well as in the ventricles. Partial volume between the cerebro-spinal fluid compartment and brain cortex might lead to an intravoxel bi-exponential behavior, because the apparent diffusion coefficient of the cerebro-spinal fluid is larger than that of the brain. In addition, caution is advised when interpreting D* in a region of interest where the perfusion compartment is vanishing, such as in a stroke, because D* becomes the pseudo-diffusion-coefficient of an “empty compartment”, is therefore not properly defined and should not be over-interpreted (12).Clinical application in the brain
In the clinical setting, the IVIM perfusion method is of interest for three main reasons: first, it permits to acquire perfusion information without injection of contrast agent, which is of particular interest in the context of recent discoveries of gadolinium deposition in various part of the brain after repeated i.v. gadolinium-based contrast injection (13-16); second, the IVIM method is essentially local, in the sense that because both excitation and read-out are done in the same plane, the method is independent of the path the blood takes to reach the voxel. This might be of particular interest for example in the brain in cases of slow blood flow, such as in cerebral stroke or severe carotid artery stenosis, in which local blood flow might be nevertheless conserved through appropriate collaterals; and third, because the methodology is essentially different than other perfusion methods, it might provide additional and complementary perfusion information, not available otherwise. The currently two main clinical applications of perfusion imaging in the brain are stroke and oncology. In stroke, a significant decrease in f was measured in the infarcted area compared to the contralateral hemisphere (12,17,18). In addition, in two patients with cerebral brain death, lack of cerebral perfusion could be demonstrated with IVIM (19), in accordance with findings with other modalities (20). In adult brain oncology, gliomas are the most frequent primary brain tumors, and account for 70% of adult malignant primary brain tumors (21). They are graded for malignity using the WHO classification, and an essential component of high grade gliomas compared to low grade, is the aspect and density of the microvasculature, with important abnormalities in high-grade gliomas, including irregular, leaky vessels and disordered network structure (22). Accordingly, a significant increase in the perfusion fraction f was observed in high grade gliomas compared to low grade (23-25). Lymphomas are the second most frequent brain tumor, and account for 3–5% of primary brain tumors (21), and are made of densely packed immune cells (usually B-cells), and with consequently low perfusion. Accordingly, a significant decrease in f has been observed in brain lymphoma compared to normal brain parenchyma (26,27), and this suggest that IVIM can be of help to discriminate high grade gliomas from lymphomas. Further and interestingly, patients with an initial increased perfusion fraction in glioblastoma were found to have diminished survival (28,29), suggesting f might be of additional value to histology in the prognosis of high grade brain gliomas. In more advanced applications, IVIM might be of particular interest to probe perfusion in diseases of the microvasculature, such as cerebral small vessel disease (30-32).