Reinoud P. H. Bokkers

Arterial spin labeling perfusion MRI at multiple delay times: a correlative study with H215O positron emission tomography in patients with symptomatic carotid artery occlusion

Arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) with image acquisition at multiple inversion times is a noninvasive ASL technique able to compensate for spatial heterogeneities in transit times caused by collateral blood flow in patients with severe stenosis of the cerebropetal blood vessels. Our aim was to compare ASL-MRI and H215O positron emission tomography (PET), the gold standard for cerebral blood flow (CBF) assessment, in patients with a symptomatic internal carotid artery (ICA) occlusion. Fourteen patients (63±14 years) with a symptomatic ICA occlusion underwent both ASL-MRI and H215O PET. The ASL-MRI was performed using a pulsed STAR labeling technique at multiple inversion times within 7 days of the PET. The CBF was measured in the gray-matter of the anterior, middle and posterior cerebral artery, and white-matter. Both PET and ASL-MRI showed a significantly decreased CBF in the gray-matter of the middle cerebral artery in the hemisphere ipsilateral to the ICA occlusion. The average gray-matter CBF measured with ASL-MRI (71.8±4.3 mL/min/100 g) was higher (P<0.01) than measured with H215O PET (43.1±1.0 mL/min/100 g). In conclusion, ASL-MRI at multiple TIs is capable of depicting areas of regions with low CBF in patients with an occlusion of the ICA, although a systematic overestimation of CBF relative to H215O PET was noted.

Intra- and Multicenter Reproducibility of Pulsed, Continuous and Pseudo-Continuous Arterial Spin Labeling Methods for Measuring Cerebral Perfusion

Intra- and multicenter reproducibility of currently used arterial spin labeling (ASL) methods were assessed at three imaging centers in the Netherlands, equipped with Philips 3TMR scanners. Six healthy participants were scanned twice at each site. The imaging protocol consisted of continuous ASL (CASL), pseudo-continuous ASL (p-CASL) with and without background suppression, pulsed ASL (PASL) with single and multiple inversion times (TIs), and selective ASL for segmentation. Reproducibility was expressed in terms of the coefficient of repeatability and the repeatability index. Voxelwise analysis of variance was performed, yielding brain maps that reflected regional variability. Intra- and multicenter reproducibility were comparable for all methods, except for single TI PASL, with better intracenter reproducibility (F-test of equality of two variances, P < 0.05). Pseudo-continuous ASL and multi TI PASL varied least between sites. Variability maps of all methods showed most variability near brain-feeding arteries within sessions and in gray matter between sessions. On the basis of the results of this study, one could consider the use of reference values in clinical routine, with whole-brain p-CASL perfusion varying < 20% over repeated measurements within the same individuals considered to be normal. Knowledge on regional variability allows for the use of perfusion-weighted images in the assessment of local cerebral pathology.

Whole-Brain Arterial Spin Labeling Perfusion MRI in Patients With Acute Stroke

Background and Purpose— Perfusion MRI can be used to identify patients with acute ischemic stroke who may benefit from reperfusion therapies. The risk of nephrogenic systemic fibrosis, however, limits the use of contrast agents. Our objective was to evaluate the ability of arterial spin labeling (ASL), an alternative noninvasive perfusion technique, to detect perfusion deficits compared with dynamic susceptibility contrast (DSC) perfusion imaging. Methods— Consecutive patients referred for emergency assessment of suspected acute stroke within a 7-month period were imaged with both ASL and DSC perfusion MRI. Images were interpreted in a random order by 2 experts blinded to clinical information for image quality, presence of perfusion deficits, and diffusion–perfusion mismatches. Results— One hundred fifty-six patients were scanned with a median time of 5.6 hours (range, 3.0–17.7 hours) from last seen normal. Stroke diagnosis was clinically confirmed in 78 patients. ASL and DSC imaging were available in 64 of these patients. A perfusion deficit was detected with DSC in 39 of these patients; ASL detected 32 of these index perfusion deficits, missing 7 lesions. The median volume of the perfusion deficits as determined with DSC was smaller in patients who were evaluated as normal with ASL than in those with a deficit (median [interquartile range], 56 [10–116] versus 114 [41–225] mL; P=0.01). Conclusions— ASL can depict large perfusion deficits and perfusion–diffusion mismatches in correspondence with DSC. Our findings show that a fast 2½-minute ASL perfusion scan may be adequate for screening patients with acute stroke with contraindications to gadolinium-based contrast agents.

Arterial Spin-Labeling MR Imaging Measurements of Timing Parameters in Patients with a Carotid Artery Occlusion

BACKGROUND AND PURPOSE: Arterial spin-labeling (ASL) with image acquisition at multiple delay times can be exploited in perfusion MR imaging to visualize and quantify the temporal dynamics of arterial blood inflow. In this study, we investigated the consequences of an internal carotid artery (ICA) occlusion and collateral blood flow on regional timing parameters. MATERIALS AND METHODS: Seventeen functionally independent patients with a symptomatic ICA occlusion (15 men, 2 women; mean age, 57 years) and 29 sex- and age-matched control subjects were investigated. ASL at multiple delay times was used to quantify regional cerebral blood flow (CBF) and the transit and trailing edge times (arterial timing parameters) reflecting, respectively, the beginning and end of the labeled bolus. Intra-arterial digital subtraction angiography and MR angiography were used to grade collaterals. RESULTS: In the hemisphere ipsilateral to the ICA occlusion, the CBF was lower in the anterior frontal (31 ± 4 versus 47 ± 3 mL/min/100 g, P < .01), posterior frontal (39 ± 4 versus 55 ± 2 mL/min/100 g, P < .01), and frontal parietal region (49 ± 3 versus 61 ± 3 mL/min/100 g, P = .04) than that in control subjects. The trailing edge of the frontal-parietal region was longer in the hemisphere ipsilateral to the ICA occlusion compared with that in control subjects (2225 ± 167 versus 1593 ± 35 ms, P < .01). In patients with leptomeningeal collateral flow, the trailing edge was longer in the anterior frontal region (2436 ± 275 versus 1648 ± 201 ms, P = .03) and shorter in the occipital region (1815 ± 128 versus 2388 ± 203 ms, P = .04), compared with patients without leptomeningeal collaterals. CONCLUSION: Regional assessment of timing parameters with ASL may provide valuable information on the cerebral hemodynamic status. In patients with leptomeningeal collaterals, the most impaired territory was found in the frontal lobe.

Symptomatic Carotid Artery Stenosis: Impairment of Cerebral Autoregulation Measured at the Brain Tissue Level with Arterial Spin-labeling MR Imaging

PURPOSE To measure the cerebral autoregulatory status of the brain tissue supplied by the individual brain-feeding arteries in patients with symptomatic stenosis of the internal carotid artery (ICA) by using arterial spin-labeling (ASL) magnetic resonance (MR) imaging and to compare this status with that in healthy controls. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Twenty-three patients (mean age, 69.3 years +/- 8.0 [standard deviation]) with unilateral symptomatic stenosis of the ICA and 20 healthy controls (mean age, 66.8 years +/- 6.3 [standard deviation]) underwent perfusion and flow territory-selective ASL MR imaging before and after intravenous administration of acetazolamide. Cerebrovascular reactivity was measured throughout the brain in the gray matter that is supplied by the individual ICAs and the basilar artery. Data were analyzed with paired and unpaired t tests. RESULTS In patients with symptomatic stenosis of the ICA, the flow territory of the symptomatic ICA was smaller than that of the asymptomatic ICA. After administration of acetazolamide, a significant increase in cerebral blood flow at the brain tissue level was measured in both control subjects and patients in all perfusion territories. Mean cerebrovascular reactivity values were 35.9% +/- 3.0% (standard error) and 44.6% +/- 3.5% (standard error) in the flow territories of the patients with symptomatic ICAs and those with asymptomatic ICAs, respectively, and 47.9% +/- 3.1% (standard error) in the control subjects. Cerebrovascular reactivity was lower in the flow territory of the symptomatic ICA than in the arteries of control participants (mean difference, -12.0%; 95% confidence interval: -20.7%, -3.3%). CONCLUSION In patients with symptomatic stenosis of the ICA, vasodilatory capacity in the flow territories of the major cerebral arteries can be visualized and quantified at the brain tissue level with ASL MR imaging.

Noninvasive MR imaging of cerebral perfusion in patients with a carotid artery stenosis

Background: Arterial spin labeling (ASL) perfusion MRI with image acquisition at multiple delay times can be used to measure delays in the arrival of arterial blood to the brain. We assessed the effect of a symptomatic internal carotid artery (ICA) stenosis on ASL timing parameters, and evaluated the effect of collateral flow through the circle of Willis. Methods: Forty-four functionally independent patients (30 men, 69 ± 9 years) with a recently symptomatic ICA stenosis ≥50% and 34 sex-matched and age-matched healthy volunteers were investigated. Magnetic resonance angiography and 2-dimensional phase-contrast imaging were used to assess collateral flow in the circle of Willis. Results: In the hemisphere ipsilateral to the ICA stenosis, cerebral blood flow (CBF) was lower (p < 0.01) in the anterior frontal, posterior frontal, parieto-occipital, and occipital regions than in control subjects. The transit times were prolonged (p < 0.01) in the ipsilateral anterior frontal, posterior frontal, and frontoparietal regions when compared with the control subjects. The trailing edge time was prolonged (p < 0.01) in the ipsilateral frontoparietal region when compared to the control subjects. In the 27 patients without a contralateral stenosis, the trailing edge was longer (p < 0.01) in the ipsilateral posterior frontal, frontoparietal, and parieto-occipital regions than in the contralateral regions. Collateral flow via the circle of Willis did not affect CBF and transit or trailing edge times. Conclusion: Arterial spin labeling MRI is a noninvasive tool for imaging cerebral blood flow and delays in the arrival of arterial blood to the brain, and can potentially provide valuable information on the quality of perfusion to the brain in patients with cerebrovascular disease.

Mapping of cerebral perfusion territories using territorial arterial spin labeling: techniques and clinical application

A knowledge of the exact cerebral perfusion territory which is supplied by any artery is of great importance in the understanding and diagnosis of cerebrovascular disease. The development and optimization of territorial arterial spin labeling (T‐ASL) MRI techniques in the past two decades have made it possible to visualize and determine the cerebral perfusion territories in individual patients and, more importantly, to do so without contrast agents or otherwise invasive procedures. This review provides an overview of the development of ASL techniques that aim to visualize the general cerebral perfusion territories or the territory of a specific artery of interest. The first efforts of T‐ASL with pulsed, continuous and pseudo‐continuous techniques are summarized and subsequent clinical studies using T‐ASL are highlighted. In the healthy population, the perfusion territories of the brain‐feeding arteries are highly variable. This high variability requires special consideration in specific patient groups, such as patients with cerebrovascular disease, stroke, steno‐occlusive disease of the large arteries and arteriovenous malformations. In the past, catheter angiography with selective contrast injection was the only available method to visualize the cerebral perfusion territories in vivo. Several T‐ASL methods, sometimes referred to as regional perfusion imaging, are now available that can easily be combined with conventional brain MRI examinations to show the relationship between the cerebral perfusion territories, vascular anatomy and brain infarcts or other pathology. Increased availability of T‐ASL techniques on clinical MRI scanners will allow radiologists and other clinicians to gain further knowledge of the relationship between vasculature and patient diagnosis and prognosis. Treatment decisions, such as surgical revascularization, may, in the near future, be guided by information provided by T‐ASL MRI in close correlation with structural MRI and quantitative perfusion information. Copyright

Cerebrovascular reactivity within perfusion territories in patients with an internal carotid artery occlusion

Background Arterial spin labelling (ASL) is an MRI technique for measuring perfusion at the brain tissue level. The aim of the study was to investigate cerebrovascular reactivity (CVR) at brain-tissue level in patients with an internal carotid artery (ICA) occlusion by combining ASL-MRI with a vascular challenge, and determine whether the CVR varies within the perfusion territory of the brain-feeding arteries. Methods Sixteen patients with a symptomatic ICA occlusion and 16 age-matched healthy control subjects underwent perfusion and perfusion-territory selective ASL-MRI before and after acetazolamide administration. CVR was assessed throughout the brain in the grey matter supplied by the unaffected asymptomatic ICA and the basilar artery. Results Cerebral blood flow increased (p<0.01) in all perfusion territories after acetazolamide in the patients and controls. In the tissue supplied by the unaffected contralateral ICA, CVR was lower in the tissue supplied by the unaffected contralateral ICA in the patients when compared with the controls (22.8±16.1 vs 54.2±13.1%; mean difference, −31.5%, 95% CI −42.1 to −20.8). Within the perfusion territory of the unaffected ICA, the CVR was lower in the brain tissue on the side of the occluded ICA than on the side of the unaffected ICA (13.5±20.4 vs 26.2±16.0%; paired mean difference −12.5%, 95% CI −20.3 to −4.7). Conclusion ASL-MRI can assess impaired cerebrovascular reactivity at the brain-tissue level in patients with a symptomatic ICA occlusion. Assessment of CVR with ASL-MRI may help to identify the tissue most at risk for future stroke and as such may guide medical treatment.

Robustness and reproducibility of flow territories defined by planning-free vessel-encoded pseudocontinuous arterial spin-labeling.

SUMMARY: Flow-territory mapping by MR imaging ASL noninvasively provides a unique insight into the distribution of cerebral perfusion. The introduction of planning-free vessel-encoded pCASL made flow-territory mapping feasible for clinical use, though lack of individual planning could impede reproducibility of this technique. We assessed the reproducibility of planning-free vessel-encoded pCASL in patients and controls. Results indicated that planning-free vessel-encoded pCASL is a reproducible method that could assist in clinical decision-making.

Pseudocontinuous Arterial Spin Labeling Quantifies Relative Cerebral Blood Flow in Acute Stroke

Background and Purpose— The aim of this study was to test whether arterial spin labeling (ASL) can detect significant differences in relative cerebral blood flow (rCBF) in the core, mismatch, and reverse-mismatch regions, and whether rCBF values measured by ASL in those areas differ from values obtained using dynamic susceptibility contrast (DSC) MRI. Methods— Acute stroke patients were imaged with diffusion-weighted imaging (DWI) and perfusion-weighted imaging (ASL and DSC) MRI. An expert reader segmented the ischemic lesion on DWI and the DSC time-to-peak (TTP) maps. Three regions were defined: core (DWI+, TTP+), mismatch (DWI−, TTP+), and reverse-mismatch (DWI+, TTP−). For both ASL and DSC, rCBF maps were created with commercially available software, and the ratio was calculated as the mean signal intensity measured on the side of the lesion to that of the homologous region in the contralateral hemisphere. Values obtained from core, mismatch, and reverse-mismatch were used for paired comparison. Results— Twenty-eight patients were included in the study. The mean age was 65.6 (16.9) years, with a median baseline National Institutes of Health Stroke Scale score of 10 (interquartile range, 4–17). Median time from last known normal to MRI was 5.7 hours (interquartile range, 2.9–22.6). Mean rCBF ratios were significantly higher in the mismatch 0.53 (0.23) versus the core 0.39 (0.33) and reverse-mismatch 0.68 (0.49) versus the core 0.38 (0.35). Differences in rCBF measured with DSC and ASL were not significant. Conclusions— ASL allows for the measurement of rCBF in the core and mismatch regions. Values in the mismatch were significantly higher than in the core, suggesting there is potential salvageable tissue.