Stroke is a leading cause of mortality and morbidity worldwide and arises from diverse intracranial wall pathologies such as intracranial atherosclerotic disease (ICAD), vasculitis, and dissection. High-resolution black-blood MR using variable-flip-angle 3D fast spin-echo, namely SPACE, VISTA or XETA, has emerged as a promising imaging technique to assess intracranial wall abnormalities [1-4]. In many of previous studies, gadolinium-based MR contrast medium was used to specifically highlight wall lesions which are sometimes unclear on pre-contrast vessel wall images in part due to the suboptimal lesion-to-wall contrast. A whole-brain inversion-recovery prepared SPACE (IR-SPACE) sequence has recently been developed in order to improve vessel wall delineation and lesion identification by substantially enhanced T1 contrast weighting and cerebrospinal fluid (CSF) attenuation. To test the hypothesis that IR-SPACE may be used for stroke etiology assessment in a non-contrast fashion, in this work, we evaluated the lesion-to-wall contrast on pre-contrast IR-SPACE images from a group of stroke and transient ischemic attack (TIA) patients.Sequence IR-SPACE is implemented on the basis of a commercial SPACE sequence. A non-selective hard RF pulse is used for excitation to achieve whole-brain coverage. This allows the TE to reduce, thus increasing both T1-weighting and SNR. To further suppress CSF signals and enhance vessel wall delineation, a flip-down RF pulse module is applied immediately after each refocusing pulse train, in effect serving as an IR preparation. Elliptical k-space sampling and long echo train length (ETL) are used to expedite data acquisition. Overall image SNR is preserved by using a experimentally-optimized flip angle series. Patient study The new sequence is currently being evaluated in a prospective clinical study which involves high resolution 3D time-of-flight (TOF) MRA and pre-/post-contrast IR-SPACE imaging. For this work, in order to accurately characterize the signal intensity of culprit lesions, a subgroup of patients (n = 12, 9 males 3 females, age range 31-74 years) was selected if: they had recent stroke or TIA; cardiogenic stroke mechanisms had been excluded; they had stenosis of at least 50%, aneurysm, or thrombosis in a large intracranial artery based on preceding computed tomographic angiography (CTA). Imaging was conducted on a 3T system (Verio, Siemens) with a 32-channel head coil. Imaging parameters for IR-SPACE imaging were: 3D sagittal orientation; TR/TE 900/15ms; spatial resolution 0.53×0.53×0.53mm3; GRAPPA factor 2; ETL 52; T1/T2 used for flip angle calculation 1100/170ms; signal average 1; scan time 8min. Data analysis Using TOF images as the reference, vessel wall lesion was identified on both pre- and post-contrast IR-SPACE images. For focal lesions, the signal intensities (S) of the lesion and neighboring normal vessel wall were measured. Lesion-to-wall contrast ratio was calculated as Slesion/Swall x 100%.Among the 12 patients, 9 had ICAD, 2 had aneurysm, and 1 had dissection-induced thrombosis respectively. Involved arterial segments were vertebral artery (5), basilar artery (1), and middle cerebral artery (6). In the ICAD patients, one patient had non-diagnostic pre-contrast IR-SPACE and one patient had non-diagnostic post-contrast IR-SPACE due to severe motion artifacts. For all the atherosclerotic lesions, lesion-to-wall contrast ratio was 210.0±28.7% on pre-contrast IR-SPACE and 337.7±111.5% on post-contrast IR-SPACE (Fig. 1). Such high contrast ratio on pre-contrast images made the lesions easily identified (Fig. 2-4). Aneurysm and dissection were identified on pre-contrast IR-SPACE according to their unique geometry. Furthermore, the thrombi associated with one of aneurysms or dissection were readily detectable due to the methemoglobin-mediated high T1-signal. One of the patients with aneurysm also demonstrated diffuse high-signal throughout large vessels as well as focal stenosis in small middle cerebral arterial segments (Fig. 5) Three types of intracranial arterial wall pathologies were detectable on pre-contrast IR-SPACE. We specifically quantified the lesion-to-wall contrast ratio of all atherosclerotic lesions on pre-contrast IR-SPACE images. The high contrast ratio at the pre-contrast state, although not as high as in the post-contrast state, was over 200% and thus made lesions easily identified. The high signal from the lesions may indicate the presence of intraplaque hemorrhage or lipid core, both of which are signs of plaque vulnerability according to carotid plaque studies. The contrast ratio may correlate with the symptom severity or indicate the risk of future events. In addition, the whole-brain technique was shown to have the potential to reveal multiple lesions, in effect providing a vessel wall pathology roadmap. To further elucidate whether these findings would be clinically relevant, a large-scale patient study is being conducted. Whole-brain IR-SPACE offers high lesion-to-wall contrast ratio in intracranial arterial wall pathologies. It is a promising technique for evaluating cerebrovascular disease without the use of contrast media.