Time-resolved angiography using inflow subtraction (TRAILS).

The gold standard for time-resolved intravascular angiography is digital subtraction angiography (DSA) (1,2). It is a dynamic study, providing information about cerebral hemodynamics. DSA provides high spatial and temporal resolution information about the cerebral vasculature, and allows selective interrogation of intracranial arteries, which is important for delineating the specific arterial supply of intracranial vascular lesions. However, DSA is an invasive method associated with certain risks, such as strokes, adverse reactions to iodized contrast agents, exposure to ionizing radiation, and risks associated with arterial puncture. Also, during a DSA exam, the injected tracer volume and pressure may modify the regular intravascular flow pattern and change the appearance of certain vascular structures, which ultimately could lead to a distorted representation of a vessel and blood-flow properties (3–5). Time-of-flight MRA (TOF-MRA) is performed widely for noninvasive assessment of the intracerebral vascular abnormalities including arterial stenosis, dissections, aneurysms, and arteriovenous malformations or fistulas (6,7). However, it is not a dynamic study: it does not provide any temporal information, which is important for the diagnosis of delayed flow and arteriovenous shunting. While hemodynamic information can be extracted from phase-contrast MRA velocity data, this technique has not gained wide acceptance clinically due to its long acquisition times. During the last decade, time-resolved, contrast-enhanced (CE)-MRA has been introduced as a lower resolution but minimal-invasive alternative to DSA. It has the advantage over DSA of providing cross-sectional anatomical information from structural MRI sequences performed during the same examination (8). However, the temporal resolution (usually in the order of seconds) of CE-MRA is constrained by the intravascular dynamics of the first pass of the contrast agent, as well as the short arterio-venous transit time that leads to early venous enhancement. In addition, CE-MRA requires intravenous injection of gadolinium-based contrast agents, which is contraindicated in patients with poor renal function due to the risk of nephrogenic systemic fibroses (9). Hence, a fast non-CE time-resolved MRA technique is desired as a noninvasive and nonionizing alternative to DSA. Until now such methods were either limited by long acquisition times or the use of exogenous, gadolinium-based contrast agents, precluding their use in patients with significant renal impairment. A nascent MR angiographic method that addresses these needs utilizes arterial spin labeling (ASL) principles to provide time-resolved imaging of the intracranial vasculature without the need for an exogenous contrast agent. The ASL-based angiographic image formation is usually based on two magnetization preparation states, in which blood magnetization is either inverted (“label” state) or left unperturbed (“control” state). Previously, various static ASL-based angiography methods have been proposed for imaging of the cerebral vasculature using fast readout methods, such as echo planar imaging (EPI), TrueFISP, or fast spin echo (FSE), which follow the magnetization preparation module to image the tagged blood while it is still in the arteries (10–13). Recently, pseudo-continuous arterial spin labeling (PCASL)-based time-resolved magnetic resonance angiography (MRA) strategies have been presented in which the preparation module is followed by a multiphase readout, allowing one to extract important hemodynamic information such as blood arrival and transit times. Alternatively to a multiphase readout, one can use multiple acquisitions subsequent to preparation modules with varying tagging durations or varying posttagging delays to retrieve hemodynamic information (14–22). Depending on the readout and labeling strategy, targeting of a specific vessel of interest for angiographic purposes is also possible. In theory, the spatial or temporal resolution of PCASL-based angiography is only restricted by the scan time or TR unlike CE-MRA. However, in practice due mostly to scan time limitations previous studies achieved only low temporal resolution, >150 ms, or necessitated compromise where higher temporal resolution was traded for a high temporal footprint. For the same reason, some of the previous studies were limited to two-dimensional (2D) projection imaging or used restricted coverage/small field of views. Some PCASL-based MRA studies also relied on time-consuming gating to avoid flow-related pulsation artifacts or complete signal voids that might arise if a balanced-steady-state free precession (SSFP) readout is used, which could emanate from fast changing, retrograde, or turbulent flow (23). Here, we present a novel variant of PCASL-based time-resolved MRA, Time-Resolved Angiography using InfLow Subtraction (TRAILS), which enables whole head coverage and the acquisition of both static (akin to TOF-MRA) and dynamic MR angiograms with a high spatial and temporal resolution in a single scan. It uses a fast 3D cones readout (24). Due to its high readout duty cycle and short echo times, the 3D cones readout is signal-to-noise ratio (SNR) and scan time efficient; has good flow compensation properties and has support for asymmetric field of views (FOVs). Whole-brain TRAILS can be achieved within clinically feasible scan times of less than 5 min without using gating or parallel imaging. First proof-of-principle studies of intravascular arteries have been conducted in healthy volunteers to demonstrate the feasibility of this novel method.