Distribution of cerebral blood flow in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery stenosis

Fifty-three subjects were included prospectively in the study. Thirty-five were functionally independent patients with a unilateral ICA stenosis of ≥50% and 18 were healthy control subjects. Of the patients, 20 had an asymptomatic ICA stenosis (12 males and 8 females; mean age ± SD, 69 ± 7 years) and 15 a symptomatic stenosis (9 male, 6 female; 71 ± 7 years). The symptomatic patients had experienced a transient ischemic attack (TIA), non-disabling ischemic stroke, or amaurosis fugax on the side of the stenosis in the 3 months before inclusion and were seen at our hospital for diagnosis and treatment. The patients with an asymptomatic ICA stenosis were recruited from a hospital-based vascular screening study involving subjects with risk factors for atherosclerosis or clinically manifest atherosclerotic vessel disease [12]. Stenoses of the ICAs were measured with color Doppler-assisted Duplex ultrasonography and peak systolic velocity thresholds based on literature were used for the diagnosis of less than 50%, 50% to 70% or 70% to 99% stenoses [13]. The control group consisted of 18 healthy age and sex-matched volunteers (11 male, 7 female; 67 ± 7 years). All control subjects were recruited through local media advertisements and did not have a history of neurological disease or vascular pathology on MRI or MR angiography (MRA) of the brain. Subjects with diabetes mellitus or severe renal or liver dysfunction were excluded.

Each subject underwent an MRI investigation on a clinical 3 Tesla MRI system (Achieva, Philips Medical Systems, The Netherlands) equipped with an eight-element phased-array head coil and locally developed software for ASL-MR imaging. To depict the perfusion territories of the ICAs and the basilar artery, territory specific perfusion images were acquired with a pseudo-continuous selective ASL perfusion sequence, according to a previously published protocol [14, 15]. To position the imaging section, a T₁-weighted spin-echo sequence was first obtained in the sagittal plane. Seventeen 7 mm slices with no slice gap were subsequently aligned parallel to the orbito-meatal angle, as shown in Fig. 1a. Labeling was performed by employing a train of 18°, 0.5 ms, Hanning-shaped radiofrequency pulses at an interpulse pause of 0.5 ms, for a duration of 1,650 ms, in combination with a balanced gradient scheme [16, 17]. The control situation, without labeling of arterial blood, was achieved by adding 180° to the phase of all even RF pulses. Perfusion territory selective ASL-MRI was accomplished through manipulating the spatial labeling efficiency by applying additional gradients between the labeling pulses in sets of 5 dynamics as demonstrated in Fig. 1b. Imaging was performed with single-shot echo planar imaging in combination with parallel imaging (SENSE factor 2.5) and background suppression. The background suppression consisted of a saturation pulse immediately before labeling and inversion pulses at 1,680 and 2,830 ms after the saturation pulse, 1,525 ms after the labeling stopped [18]. The following parameters were used: repetition time (TR), 4,000 ms; echo time (TE), 14 ms; field of view (FOV), 240 × 140 mm; matrix size, 89 × 79; 75 dynamics; scan time, 5½ min.

A three-dimensional time-of-flight MR angiography was made with subsequent maximum intensity projection reconstruction using the following parameters: TR/TE, 30/6.9 ms; flip angle 20°; 2 averages; FOV, 100 × 100 mm; matrix, 256 × 256; 50 slices; slice thickness, 1.2 mm with 0.6 mm overlap; scan time, 3 min. Collateral blood flow direction was determined according to a previously published imaging protocol with 2 consecutive 2-dimensional phase-contrast MRI measurements, out of which one was phase-encoded in the anterior-posterior direction and one in the right-left direction (TR/TE, 9.4/5.9 ms; flip angle, 7.5º; FOV, 250 × 187.5; single slice, 8 averages; slice thickness, 13 mm; velocity sensitivity, 40 cm/s; scan time, 20 s) [19].

The decision whether the caudate nucleus, lentiform nucleus and thalamus were supplied by the ipsilateral ICA, the contralateral ICA or the basilar artery was made by one author (NH), blinded to the MR angiography images, on the perfusion territory selective ASL-MR images. For this purpose the perfusion territories of the left ICA, right ICA and basilar artery were first identified using k-means clustering with Matlab (The MathWorks, Natick, Mass, version 7.5) [20]. Perfusion contributions were then scored by evaluating the head portion of the caudate nucleus, the entire lentiform nucleus, and entire thalamus. The ventricular system, anterior limb and posterior limb of the internal capsule, and external capsule were used to delineate the deep brain structures.

The morphology of the circle of Willis and the direction of blood flow through the primary collaterals were determined separately, blinded to the perfusion territory selective ASL-MR images, with the time-of-flight and phase-contrast MR angiography images. Anterior collateral flow was defined as blood flow across the anterior communicating artery with retrograde flow in the precommunicating part of the anterior cerebral artery (A1 segment) ipsilateral to the stenosis. Posterior-to-anterior blood flow in the posterior communicating artery was considered to represent posterior collateral flow. Each circle of Willis was assessed for a missing or hypoplastic A1 segment and for the presence of a fetal-type posterior communicating artery, of which the diameter is larger than the precommunicating segment of the ipsilateral posterior cerebral artery.