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Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease
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Journal of Neuroradiology (2016) xxx, xxx—xxx
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ORIGINAL ARTICLE
Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease Nolan S. Hartkamp a, Reinoud P.H. Bokkers a, M.J.P. van Osch b, Gert J. de Borst c, Jeroen Hendrikse a,∗ a
Room E01.132, Department of Radiology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands b Department of Radiology, C.J. Gorter Institute of High-Field MRI, Leiden University Medical Center, Leiden, The Netherlands c Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
KEYWORDS Magnetic resonance imaging; Perfusion; Cerebrovascular reactivity; Carotid artery disease
Summary Background and purpose: To assess the effect of unilateral large vessel disease upon the cerebral hemodynamic autoregulatory status in the basal ganglia of patients with steno-occlusive internal carotid artery (ICA) disease. Materials and methods: Twenty-five healthy volunteers and 38 patients with a unilateral symptomatic steno-occlusive ICA lesion and were investigated; 20 with a stenosis > 50% and 18 with an occlusion. Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were assessed with pseudo-continuous arterial spin labeling (ASL) magnetic resonance (MR) imaging before and after administration of acetazolamide. Results: When compared to controls, the CVR in patients with ICA stenosis was significantly lower in the middle cerebral artery (MCA) territory (P < 0.05), and in the caudate (P < 0.05) and lentiform nucleus (P < 0.05) of the hemisphere ipsilateral to the stenosis. The CVR in the caudate nucleus contralateral to the stenosis was significantly lower (P < 0.05) as well. In patients with ICA occlusion, the CVR in the hemisphere ipsilateral to the occlusion as well as in the contralateral hemisphere was significantly lower in the MCA territory (P < 0.05), the caudate (P < 0.05) and lentiform nucleus (P < 0.05), and in the thalamus (P < 0.05). Conclusion: Perfusion ASL MR imaging shows impaired cerebral hemodynamic autoregulation of the basal ganglia in patients with steno-occlusive ICA disease both in the hemisphere ipsilateral as well as in the hemisphere contralateral to the stenosis or occlusion. © 2016 Elsevier Masson SAS. All rights reserved.
Abbreviations: ASL, arterial spin labeling; CBF, cerebral blood flow; CVR, cerebrovascular reactivity; ICA, internal carotid artery; MCA, middle cerebral artery; RF, radiofrequency; ROI, region of interest; SEM, standard error of mean. ∗ Corresponding author. Tel.: +31 88 755 6687; fax: +31 30 258 1098. E-mail address: [email protected] (J. Hendrikse). http://dx.doi.org/10.1016/j.neurad.2016.07.003 0150-9861/© 2016 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Hartkamp NS, et al. Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease. J Neuroradiol (2016), http://dx.doi.org/10.1016/j.neurad.2016.07.003
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Introduction Up to one-fourth of all first ischemic cerebral infarcts are subcortical [1]. Subcortical ischemia is classically associated with thickened vessel walls (lipohyalinosis), endothelial dysfunction and impaired hemodynamic autoregulation of the perforating arteries leading to a decreased perfusion [2,3]. Normally, cerebral blood flow (CBF) is sustained by autoregulation through constriction and vasodilatation of the resistance arterioles [4]. Cerebrovascular reactivity (CVR) is however reduced in patients with a recent cerebral ischemic event [5]. Functional measures of vasodilatory capacity such as CVR have long been interesting imaging targets to visualize cerebral hemodynamic compromise [6]. Studies however have been mostly focused on CVR in cortical areas. In patients with large vessel disease, it is unknown whether the stenosis or occlusion of the carotid artery also affects CVR of the basal ganglia. There are various strategies to assess CVR. Each relies on measuring blood flow in a major cerebral artery or perfusion of brain tissue before and after a vasodilatory stimulus [7—11]. Techniques focusing on brain tissue perfusion provide the most detail, but often require ionizing radiation or contrast agents. Arterial spin labeling (ASL) is a noninvasive magnetic resonance (MR) perfusion technique for imaging whole-brain cerebral perfusion [12—14]. Instead of contrast agents, it uses radiofrequency pulses to magnetically label arterial blood. Perfusion measurements in brain tissue are fairly straightforward to perform before and after a vascular challenge such as the administration of acetazolamide [15,16]. Recently developed ASL methods combined with background suppression, such as pseudo-continuous ASL sequences [17], allow the assessment of perfusion of cortical brain areas as well as the smaller subcortical brain regions such as the basal ganglia [18—20]. The aim of this study was to compare the cerebral hemodynamic autoregulatory state of the cortical brain as well as the basal ganglia in patients with steno-occlusive disease of the internal carotid artery (ICA) with that of healthy controls by means of ASL perfusion MR imaging.
Methods and materials The study was approved by the institutional ethical review board and written informed consent was obtained from all participants.
Subjects Thirty-seven patients and 25 healthy controls were prospectively included into the study. Patients were functionally independent and had experienced a transient ischemic attack, transient monocular blindness, or non-disabling ischemic stroke ipsilateral to the side of the ICA with atherosclerotic stenosis or occlusion, and had been referred to our hospital for diagnosis and treatment. Patients with ischemic stroke were included after the subacute phase was resolved. Duplex ultrasonography of the carotid arteries and vertebral arteries was performed to diagnose and grade a potential carotid artery stenosis or occlusion based on peak
systolic velocity. If present, the stenosis or occlusion of the carotid arteries was confirmed with either a recent contrast enhanced (CE) computed tomography angiography according to the NASCET criteria. A stenosis larger than 70% was determined to be a significant stenosis [21]. Of the patients, 20 had a symptomatic ICA stenosis and 17 had an ICA occlusion. No contralateral carotid artery stenosis > 50% was present in the stenosis or occlusion patients. Three patients with an ICA stenosis and one patient with an ICA occlusion had an origin or proximal stenosis of < 50% of one vertebral artery. These patients had antegrade blood flow in both vertebral arteries confirmed with duplex ultrasonography. Patients with diabetes mellitus, severe renal or liver dysfunction, or disabling stroke, defined as a score of 3 to 5 on the modified Rankin scale, were excluded [22]. Control subjects were recruited through local media advertisements and did not have a history of neurological disease or vascular pathology on magnetic resonance imaging (MRI) or MR angiography of the brain.
Magnetic resonance imaging MRI investigations were performed on a clinical 3 Tesla MRI scanner (Achieva, Philips Medical Systems, The Netherlands) equipped with an eight-element phased-array head coil and locally developed software to enable ASL MR imaging. Each subject underwent ASL perfusion MR imaging before and 15 minutes after a vasodilatory challenge through intravenous administration of acetazolamide (Goldshield Pharmaceuticals, Croydon Surrey, United Kingdom) at a dose of 14 mg/kg body weight and a maximum dose of 1200 mg. Perfusion images were acquired using a pseudocontinuous ASL sequence [23]. Seventeen 7 mm slices were subsequently aligned parallel to the orbitomeatal angle. Labeling was performed for a duration of 1650 ms by employing a train of 18 degrees Hanning-shaped radiofrequency (RF) pulses of 0.5 ms and an interpulse pause of 0.5 ms in combination with a balanced gradient scheme [23,24]. The control situation, without labeling of arterial blood, was achieved by adding 180◦ to the phase of all even RF pulses. Imaging was performed 1525 ms after the labeling stopped with single-shot echo planar imaging in combination with parallel imaging (SENSE factor 2.5) and background suppression, which consisted of a saturation pulse immediately before labeling and inversion pulses at 1680 and 2830 ms after the saturation pulse [25]. The following parameters were used: repetition time (TR), 4000 ms; echo time (TE), 14 ms; field of view (FOV), 240 × 240 × 119 mm; matrix size, 80 × 79; pairs of controls and labels, 38; scan time, 5.5 minutes. An inversion-recovery sequence was acquired with the same geometric orientation and resolution as the ASL perfusion images to measure the magnetization of arterial blood and for anatomical segmentation purpose. A T2 -weighted fluid-attenuated inversion-recovery image was acquired to detect tissue infarction by using the following parameters: TR/TE, 11,000/125 ms; inversion time, 2800 ms; matrix size, 240 × 240; slices, 24; slice thickness, 2 mm. A threedimensional time-of-flight MR angiography was made with subsequent maximal intensity projection reconstruction
Please cite this article in press as: Hartkamp NS, et al. Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease. J Neuroradiol (2016), http://dx.doi.org/10.1016/j.neurad.2016.07.003
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Cerebrovascular reactivity in the basal ganglia of patients with carotid artery disease Table 1
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Demographic and clinical characteristics of the study population. Patients
Number Male (n [%]) Age (mean years ± SD) Degree of ICA stenosis (n) 0—49% 50—69% 70—99% Occluded Presenting events (n) Transient ischemic attack Ischemic stroke Retinal ischemia
Healthy controls
Stenosis
Occlusion
25 12 (48%) 61.8 ± 8.0
20 13 (65%) 69.0 ± 8.2
18 13 (76.5%) 55.0 ± 15.0
25 0 0 0
0 2 18 0
0 0 0 18
— — —
13 4 3
10 8 0
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 minutes. Collateral blood flow direction was determined according to a previously published imaging protocol with 2 consecutive 2-dimensional phase-contrast MRI measurements, 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, 7.5◦ ; FOV, 250 × 187.5; 8 averages; slice thickness, 13 mm; velocity sensitivity, 40 cm/s; scan time, 20 seconds) [26].
Image processing Data were analyzed with Matlab (The MathWorks, Natick, Mass, version 7.5) and SPM5 (Wellcome Trust Centre for Neuroimaging, Oxford, UK). CBF (mL·100 mL−1 ·min−1 ) was calculated from the ASL perfusion MR images according to a previously published model [27]. The T2 * of arterial blood and T1 of blood were assumed to be 50 and 1680 ms, respectively [28,29]. The water content of blood was assumed to be 0.76 mL per milliliter of arterial blood [30]. The mean resting magnetization of the blood in all subjects was determined by selecting a region of interest in the cerebrospinal fluid and iteratively fitting the inversion-recovery data according to a previously published procedure [30]. CVR was defined as the percentage of increase in CBF within 15 minutes after administration of acetazolamide. The CBF was therefore calculated at baseline and after the vasodilatory challenge in four regions of interest (ROIs), which were placed cortically in the middle cerebral artery (MCA) territory and subcortically on the head portion of the caudate nucleus, the lentiform nucleus, and the thalamus by a single observer (NSH). For placement of the ROIs a surrogate anatomical T1 -weighted image was calculated from the inversion-recovery sequence by calculating the reciprocal of the quantitative T1 . The ventricular system, anterior limb and posterior limb of the internal capsule, and external capsule were used to delineate the brain structures during the manual segmentation. Areas of hyperintensity on the FLAIR images, indicating areas of infarction, were manually
excluded from the ROIs. The T1 image was further segmented into white and gray matter probability maps with SPM5 software. Thresholding was applied to create a gray matter mask, which was combined with each ROI to avoid partial voluming of white and gray matter. For visualization purposes, the perfusion and reactivity images were spatially smoothed using a Gaussian filter.
Statistical analysis Differences in CBF and CVR values between hemispheres ipsilateral and contralateral to the symptomatic ICA were assessed for each ROI using paired t-tests. A P-value < 0.05 was considered to indicate statistical significance. Since no differences were found in CBF or CVR between the hemispheres in the control group, these values were averaged for further analysis. Increases in CBF measurements before and after administration of acetazolamide were assessed using paired t-tests. Differences in the CBF and CVR measurements between the control group and patient groups were assessed using independent t-tests. A Bonferonni correction was used for multiple comparisons. The corrected P values are reported. Values are expressed as means ± standard error of the mean (SEM) unless otherwise specified. SPSS (SPSS Inc., Chicago, Illinois, version 15) was used for statistical analysis.
Results Table 1 summarizes the demographic and clinical characteristics of the healthy controls and of the patients with an ICA stenosis or occlusion. Perfusion images before and after administration of acetazolamide together with the resulting reactivity images and FLAIR images are shown for a healthy subject (Fig. 1), a patient with an ICA stenosis (Fig. 2), and a patient with an ICA occlusion (Fig. 3). CBF values before and after the vasodilatory challenge and CVR values are summarized for the healthy controls and stenosis and occlusion patients in the regions of the MCA territory, caudate nucleus, lentiform nucleus, and thalamus (Table 2). The baseline CBF in the patients with ICA
Please cite this article in press as: Hartkamp NS, et al. Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease. J Neuroradiol (2016), http://dx.doi.org/10.1016/j.neurad.2016.07.003
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Figure 1 Case example of a 55-year-old healthy subject. Time-of-flight MR angiogram images (A) of the circle of Willis show the presence of all vessels. Images of cerebral perfusion before (B) and after (C) administration of acetazolamide, and of the cerebrovascular reactivity (D) correspond with FLAIR images from cranial (top) to caudal (bottom). The images show the superimposed outline of the regions of interest placed in the middle cerebral artery, caudate nucleus, lentiform nucleus and thalamus. The perfusion images show no evidence of reduced cerebral blood flow. The reactivity images depict the relative increase in cerebral perfusion after administration of acetazolamide.
Figure 2 Case example of a 51-year-old patient with a unilateral symptomatic right ICA stenosis (> 70%). Images (A—E) are depicted identically to Fig. 1. MRA images (A) show the presence of a hypoplastic A1 segment ipsilateral to the stenosis. The cerebral perfusion is reasonably symmetrical between both hemispheres ipsi- and contralateral to the ICA stenosis. The reactivity images however show a subtle deficit in CVR against the right (symptomatic) hemisphere, which is most pronounced subcortically in the left most reactivity image.
stenosis was comparable with that of the healthy controls. In the patients with ICA occlusion the baseline CBF was significantly lower than in the healthy controls for ipsilateral as well as the contralateral hemisphere in the MCA territory (P = 0.012, and P = 0.036 respectively), caudate nucleus (P < 0.001, and P = 0.012 respectively), and thalamus (P < 0.001, and P = 0.012 respectively). When compared to controls, the CVR in patients with ICA stenosis was significantly lower in the caudate (P = 0.006) and lentiform nucleus (P < 0.036) ipsilateral to the stenosis.
In the patients with ICA stenosis, the CVR in the caudate nucleus contralateral to the stenosis was significantly lower (P = 0.006) as well. In patients with ICA occlusion, the CVR in the hemisphere ipsilateral to the occlusion as well as in the contralateral hemisphere was significantly lower in the MCA territory (both sides P < 0.001), the caudate (both sides P < 0.001) and lentiform nucleus (both sides P < 0.001), and in the thalamus (P = 0.048, and P = 0.006 respectively). In the patients, no significant differences in CVR were found between hemispheres ipsilateral to the ICA occlusion or
Please cite this article in press as: Hartkamp NS, et al. Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease. J Neuroradiol (2016), http://dx.doi.org/10.1016/j.neurad.2016.07.003
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Cerebrovascular reactivity in the basal ganglia of patients with carotid artery disease
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Figure 3 Case example of a 50-year-old patient with a unilateral symptomatic right ICA occlusion. Images (A—E) are depicted identically to Fig. 1. The cerebral perfusion is asymmetrical between both hemispheres ipsi- and contralateral to the ICA occlusion. The reactivity images demonstrate severely reduced CVR in the right (symptomatic) hemisphere as well as decreased CVR in the left (asymptomatic) hemisphere.
Table 2
Cerebral blood flow and reactivity after administration of acetazolamide.
Region and group
Hemisphere
CBF (mL·100 mL−1 ·min−1 ) Pre-ACZ
MCA territory Healthy controls Stenosis patients Occlusion patients Caudate nucleus Healthy controls Stenosis patients Occlusion patients Lentiform nucleus Healthy controls Stenosis patients Occlusion patients Thalamus Healthy controls Stenosis patients Occlusion patients
Reactivity (%)
Post-ACZ
Both Stenosed side Contralateral side Occluded side Contralateral side
45.2 43.8 45.0 37.8 41.7
± ± ± ± ±
1.3 1.3 1.7 3.0* 1.4*
67.0 60.4 62.8 43.5 50.8
± ± ± ± ±
1.8 2.6 2.4 3.6 2.4
48.8 37.9 40.5 15.8 22.5
± ± ± ± ±
2.1 4.4 3.5 4.0*,† 4.5*,†
Both Stenosed side Contralateral side Occluded side Contralateral side
36.2 37.9 38.0 27.1 31.3
± ± ± ± ±
1.1 2.5 1.9 2.3*,† 1.7*,†
55.4 48.9 50.5 31.3 36.8
± ± ± ± ±
1.5 3.0 2.5 3.1 2.3
54.2 29.9 34.4 13.9 17.6
± ± ± ± ±
2.9 6.6* 4.5* 5.0* 4.0*,†
Both Stenosed side Contralateral side Occluded side Contralateral side
35.9 38.1 36.0 31.8 33.3
± ± ± ± ±
1.1 3.1 1.7 2.8* 1.1*
51.6 47.7 48.3 36.7 39.5
± ± ± ± ±
1.6 2.3 2.1 3.3 1.9
44.3 30.2 35.6 16.3 18.3
± ± ± ± ±
2.0 4.7* 4.1 4.1* 3.8*,†
Both Stenosed side Contralateral side Occluded side Contralateral side
48.9 44.8 48.2 37.8 41.4
± ± ± ± ±
2.1 2.9 2.6 2.1* 1.9*
79.3 70.5 75.9 54.6 59.4
± ± ± ± ±
3.0 4.0 3.3 3.3 3.1
64.4 60.7 60.2 46.1 43.8
± ± ± ± ±
3.8 5.3 4.7 6.1* 4.5*
Cerebral blood flow (CBF) before (pre-ACZ) and after (post-ACZ) administration of acetazolamide with reactivity per region of interest, patient group and hemisphere. * Significant difference between patients and healthy controls (P < 0.05). † Significant difference between symptomatic stenosis patients and occlusion patients (P < 0.05).
Please cite this article in press as: Hartkamp NS, et al. Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease. J Neuroradiol (2016), http://dx.doi.org/10.1016/j.neurad.2016.07.003
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Summary of the circle of Willis’ variations in the study population.
Anterior circulation Missing Acom or A1 segment Anterior collateral flow Posterior circulation Ipsilateral fetal type PCA Posterior-to-anterior collateral flow Vertebrobasilar system < 50% stenosis in one vertebral artery
Healthy controls
Stenosis patients
Occlusions patients
0 0
0 4
0 6
0 0
1 0
0 4
0
3
1
stenosis and the contralateral hemisphere. In patients with an ICA occlusion, the CVR was significantly lower than in stenosis patients in the MCA territory in both the ipsilateral (P = 0.006) as contralateral hemisphere (P = 0.018). The CVR in patients with an ICA occlusion was also significantly lower than in stenosis patients for the caudate (P = 0.048) and lentiform nucleus (P = 0.024) of the contralateral hemisphere.
Collateral circulation and morphology of the circle of Willis Circle of Willis’ variations are summarized in Table 3. Regarding the anterior collateral circulation in the circle of Willis there were no subjects with a missing anterior communicating artery or a missing pre-communicating segment (A1 segment) of the anterior cerebral artery. A retrograde flow in the ipsilateral A1 segment was found on phase-contrast MR angiography, indicating anterior collateral flow in the circle of Willis in four patients with an ICA stenosis and six patients with an ICA occlusion. No significant difference was found in reactivity of either hemisphere between patients with and patients without confirmed anterior collateral blood flow. Regarding the posterior collateral circulation in the circle of Willis there was one patient with an ICA stenosis found to have a missing pre-communicating segment (P1 segment) of the ipsilateral posterior cerebral artery. Four patients with an ICA occlusion had retrograde flow in the ipsilateral posterior communicating artery as found on phase-contrast MR angiography. In none of the patients with ICA stenosis retrograde flow was found in the posterior communicating artery. No significant difference was found in reactivity of either hemisphere between patients with and without confirmed posterior collateral blood flow. Regarding the vertebrobasilar circulation a < 50% stenosis of one of the vertebral arteries was present in three patients with an ICA stenosis and one patient with an ICA occlusion. In all patients an antegrade flow was found on duplex echography in the vertebrobasilar system.
Discussion In the present study, we were able to assess the hemodynamic status in the MCA territory as well as in the basal ganglia of patients with atherosclerotic steno-occlusive disease of the internal carotid artery. Atherosclerosis is a generalized disease and it is very likely that vascular
risk factors affect both the large and the small arteries. Recently, it has been suggested however that subcortical endothelial dysfunction is not only specific to small vessel disease [31]. Our findings illustrate that hemodynamic impairment distal to a carotid artery stenosis or occlusion is most likely also accompanied with hemodynamic compromise in the subcortical gray matter such as the basal ganglia. Our results are comparable with those of other studies that have investigated CBF at baseline and CVR in the basal ganglia at the brain tissue level using SPECT [32], PET [33] or ASL MRI [18,19] in healthy subjects. However, none of these studies have investigated patients with steno-occlusive carotid artery disease. In the current study population no brain tissue damage such as lacunar infarcts was present subcortically. The impaired CVR suggests though that the basal ganglia may be vulnerable to hemodynamic stroke due to ICA stenosis or occlusion. The CVR in the thalamus of the patients with ICA occlusion was also reduced compared to healthy controls. The CVR in patients with ICA stenosis was impaired in the caudate nucleus of the hemisphere contralateral to the stenosis and in patients with ICA occlusion the CVR in the contralateral hemisphere was impaired in the MCA territory, caudate and lentiform nucleus, and thalamus as well. The hemodynamic impairment in the contralateral hemisphere may indicate that the cerebral vascular compensation mechanism, such as vasodilatation of resistance arterioles, is also affected in the vasculature of the hemisphere contralateral to the carotid artery with steno-occlusive disease. A previous study showed higher prevalence of infarcts and white matter lesions in patients with ICA occlusion both ipsilateral as well as contralateral to the occlusion [34]. This is in line with the current suggestion of a more globally impaired hemodynamic status of the brain due to a unilateral ICA occlusion or stenosis. Presence of collateral flow via the circle of Willis might potentially also influence the reactivity of the contralateral hemisphere, although we did not found significant differences in the current study. Alternatively, generalized atherosclerosis in patients with carotid artery stenosis or occlusion may affect also the CVR of the contralateral hemisphere and posterior circulation in patients with carotid artery stenosis or occlusion. The employed ASL MR imaging technique has inherent limitations such as reduced sensitivity for delayed perfusion and blood flow velocity dependent labeling efficiency. To overcome underestimation of perfusion via collateral pathways, we used pseudo-continuous ASL labeling technique
Please cite this article in press as: Hartkamp NS, et al. Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease. J Neuroradiol (2016), http://dx.doi.org/10.1016/j.neurad.2016.07.003
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Cerebrovascular reactivity in the basal ganglia of patients with carotid artery disease with an effective delay time of more than 3 seconds. This delay allows the magnetically labeled blood to reach the brain tissue in patients with steno-occlusive carotid artery disease [35]. As a result of administration of acetazolamide, the blood flow increases which leads to reduced labeling efficiency and an underestimation of CBF and CVR. This effect will however be present in the healthy controls as well as in the patients with an ICA stenosis or occlusion. Another limitation is the partial volumes of grey matter and white matter within any voxel. The lower white matter ASL signal dilutes the grey matter ASL signal. To account for this, a grey matter mask was used to select voxels with maximum grey matter content. The lower amount of remaining available voxels for each ROI is reflected in the spread of the data. In the current study we did not determine the stroke etiology or investigate whether our imaging findings could potentially help establish the etiological classification. Nevertheless, CVR measurements at brain tissue level with ASL MRI can provide valuable information regarding the hemodynamic status of the basal ganglia and gray matter, and warrants further investigation in a longitudinal setting to determine if can influence the determination of stroke etiology and clinical treatment.
Conclusion Perfusion ASL MR imaging can quantitatively assess the cerebral hemodynamic autoregulation of the basal ganglia in patients with steno-occlusive carotid artery disease. Our results show that, in patients with steno-occlusive disease of the internal carotid arteries the hemodynamic autoregulation in the basal ganglia is globally impaired.
Grant support J. Hendrikse receives support from the Dutch Heart Foundation (Grant 2010B274) and European Research Council (ERC-2014-STG-637024). R.P.H. Bokkers receives support from the Dutch Heart Foundation (Grant 2013T047).
Disclosure of interest The authors declare that they have no competing interest.
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[32] Ito H, et al. Database of normal human cerebral blood flow measured by SPECT: I. Comparison between I-123-IMP, Tc99m-HMPAO, and Tc-99m-ECD as referred with O-15 labeled water PET and voxel-based morphometry. Ann Nucl Med 2006;20(2):131—8. [33] Binks AP, et al. Gray matter blood flow change is unevenly distributed during moderate isocapnic hypoxia in humans. J Appl Physiol 2008;104(1):212—7. [34] Bisschops RHC, et al. Association between impaired carbon dioxide reactivity and ischemic lesions in arterial border zone territories in patients with unilateral internal carotid artery occlusion. Arch Neurol 2003;60(2):229—33. [35] Bokkers RPH, et al. Arterial spin-labeling MR imaging measurements of timing parameters in patients with a carotid artery occlusion. AJNR Am J Neuroradiol 2008;29(9):1698—703.
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ORIGINAL ARTICLE
Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease Nolan S. Hartkamp a, Reinoud P.H. Bokkers a, M.J.P. van Osch b, Gert J. de Borst c, Jeroen Hendrikse a,∗ a
Room E01.132, Department of Radiology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands b Department of Radiology, C.J. Gorter Institute of High-Field MRI, Leiden University Medical Center, Leiden, The Netherlands c Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
KEYWORDS Magnetic resonance imaging; Perfusion; Cerebrovascular reactivity; Carotid artery disease
Summary Background and purpose: To assess the effect of unilateral large vessel disease upon the cerebral hemodynamic autoregulatory status in the basal ganglia of patients with steno-occlusive internal carotid artery (ICA) disease. Materials and methods: Twenty-five healthy volunteers and 38 patients with a unilateral symptomatic steno-occlusive ICA lesion and were investigated; 20 with a stenosis > 50% and 18 with an occlusion. Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were assessed with pseudo-continuous arterial spin labeling (ASL) magnetic resonance (MR) imaging before and after administration of acetazolamide. Results: When compared to controls, the CVR in patients with ICA stenosis was significantly lower in the middle cerebral artery (MCA) territory (P < 0.05), and in the caudate (P < 0.05) and lentiform nucleus (P < 0.05) of the hemisphere ipsilateral to the stenosis. The CVR in the caudate nucleus contralateral to the stenosis was significantly lower (P < 0.05) as well. In patients with ICA occlusion, the CVR in the hemisphere ipsilateral to the occlusion as well as in the contralateral hemisphere was significantly lower in the MCA territory (P < 0.05), the caudate (P < 0.05) and lentiform nucleus (P < 0.05), and in the thalamus (P < 0.05). Conclusion: Perfusion ASL MR imaging shows impaired cerebral hemodynamic autoregulation of the basal ganglia in patients with steno-occlusive ICA disease both in the hemisphere ipsilateral as well as in the hemisphere contralateral to the stenosis or occlusion. © 2016 Elsevier Masson SAS. All rights reserved.
Abbreviations: ASL, arterial spin labeling; CBF, cerebral blood flow; CVR, cerebrovascular reactivity; ICA, internal carotid artery; MCA, middle cerebral artery; RF, radiofrequency; ROI, region of interest; SEM, standard error of mean. ∗ Corresponding author. Tel.: +31 88 755 6687; fax: +31 30 258 1098. E-mail address: [email protected] (J. Hendrikse). http://dx.doi.org/10.1016/j.neurad.2016.07.003 0150-9861/© 2016 Elsevier Masson SAS. All rights reserved.
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Introduction Up to one-fourth of all first ischemic cerebral infarcts are subcortical [1]. Subcortical ischemia is classically associated with thickened vessel walls (lipohyalinosis), endothelial dysfunction and impaired hemodynamic autoregulation of the perforating arteries leading to a decreased perfusion [2,3]. Normally, cerebral blood flow (CBF) is sustained by autoregulation through constriction and vasodilatation of the resistance arterioles [4]. Cerebrovascular reactivity (CVR) is however reduced in patients with a recent cerebral ischemic event [5]. Functional measures of vasodilatory capacity such as CVR have long been interesting imaging targets to visualize cerebral hemodynamic compromise [6]. Studies however have been mostly focused on CVR in cortical areas. In patients with large vessel disease, it is unknown whether the stenosis or occlusion of the carotid artery also affects CVR of the basal ganglia. There are various strategies to assess CVR. Each relies on measuring blood flow in a major cerebral artery or perfusion of brain tissue before and after a vasodilatory stimulus [7—11]. Techniques focusing on brain tissue perfusion provide the most detail, but often require ionizing radiation or contrast agents. Arterial spin labeling (ASL) is a noninvasive magnetic resonance (MR) perfusion technique for imaging whole-brain cerebral perfusion [12—14]. Instead of contrast agents, it uses radiofrequency pulses to magnetically label arterial blood. Perfusion measurements in brain tissue are fairly straightforward to perform before and after a vascular challenge such as the administration of acetazolamide [15,16]. Recently developed ASL methods combined with background suppression, such as pseudo-continuous ASL sequences [17], allow the assessment of perfusion of cortical brain areas as well as the smaller subcortical brain regions such as the basal ganglia [18—20]. The aim of this study was to compare the cerebral hemodynamic autoregulatory state of the cortical brain as well as the basal ganglia in patients with steno-occlusive disease of the internal carotid artery (ICA) with that of healthy controls by means of ASL perfusion MR imaging.
Methods and materials The study was approved by the institutional ethical review board and written informed consent was obtained from all participants.
Subjects Thirty-seven patients and 25 healthy controls were prospectively included into the study. Patients were functionally independent and had experienced a transient ischemic attack, transient monocular blindness, or non-disabling ischemic stroke ipsilateral to the side of the ICA with atherosclerotic stenosis or occlusion, and had been referred to our hospital for diagnosis and treatment. Patients with ischemic stroke were included after the subacute phase was resolved. Duplex ultrasonography of the carotid arteries and vertebral arteries was performed to diagnose and grade a potential carotid artery stenosis or occlusion based on peak
systolic velocity. If present, the stenosis or occlusion of the carotid arteries was confirmed with either a recent contrast enhanced (CE) computed tomography angiography according to the NASCET criteria. A stenosis larger than 70% was determined to be a significant stenosis [21]. Of the patients, 20 had a symptomatic ICA stenosis and 17 had an ICA occlusion. No contralateral carotid artery stenosis > 50% was present in the stenosis or occlusion patients. Three patients with an ICA stenosis and one patient with an ICA occlusion had an origin or proximal stenosis of < 50% of one vertebral artery. These patients had antegrade blood flow in both vertebral arteries confirmed with duplex ultrasonography. Patients with diabetes mellitus, severe renal or liver dysfunction, or disabling stroke, defined as a score of 3 to 5 on the modified Rankin scale, were excluded [22]. Control subjects were recruited through local media advertisements and did not have a history of neurological disease or vascular pathology on magnetic resonance imaging (MRI) or MR angiography of the brain.
Magnetic resonance imaging MRI investigations were performed on a clinical 3 Tesla MRI scanner (Achieva, Philips Medical Systems, The Netherlands) equipped with an eight-element phased-array head coil and locally developed software to enable ASL MR imaging. Each subject underwent ASL perfusion MR imaging before and 15 minutes after a vasodilatory challenge through intravenous administration of acetazolamide (Goldshield Pharmaceuticals, Croydon Surrey, United Kingdom) at a dose of 14 mg/kg body weight and a maximum dose of 1200 mg. Perfusion images were acquired using a pseudocontinuous ASL sequence [23]. Seventeen 7 mm slices were subsequently aligned parallel to the orbitomeatal angle. Labeling was performed for a duration of 1650 ms by employing a train of 18 degrees Hanning-shaped radiofrequency (RF) pulses of 0.5 ms and an interpulse pause of 0.5 ms in combination with a balanced gradient scheme [23,24]. The control situation, without labeling of arterial blood, was achieved by adding 180◦ to the phase of all even RF pulses. Imaging was performed 1525 ms after the labeling stopped with single-shot echo planar imaging in combination with parallel imaging (SENSE factor 2.5) and background suppression, which consisted of a saturation pulse immediately before labeling and inversion pulses at 1680 and 2830 ms after the saturation pulse [25]. The following parameters were used: repetition time (TR), 4000 ms; echo time (TE), 14 ms; field of view (FOV), 240 × 240 × 119 mm; matrix size, 80 × 79; pairs of controls and labels, 38; scan time, 5.5 minutes. An inversion-recovery sequence was acquired with the same geometric orientation and resolution as the ASL perfusion images to measure the magnetization of arterial blood and for anatomical segmentation purpose. A T2 -weighted fluid-attenuated inversion-recovery image was acquired to detect tissue infarction by using the following parameters: TR/TE, 11,000/125 ms; inversion time, 2800 ms; matrix size, 240 × 240; slices, 24; slice thickness, 2 mm. A threedimensional time-of-flight MR angiography was made with subsequent maximal intensity projection reconstruction
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Cerebrovascular reactivity in the basal ganglia of patients with carotid artery disease Table 1
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Demographic and clinical characteristics of the study population. Patients
Number Male (n [%]) Age (mean years ± SD) Degree of ICA stenosis (n) 0—49% 50—69% 70—99% Occluded Presenting events (n) Transient ischemic attack Ischemic stroke Retinal ischemia
Healthy controls
Stenosis
Occlusion
25 12 (48%) 61.8 ± 8.0
20 13 (65%) 69.0 ± 8.2
18 13 (76.5%) 55.0 ± 15.0
25 0 0 0
0 2 18 0
0 0 0 18
— — —
13 4 3
10 8 0
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 minutes. Collateral blood flow direction was determined according to a previously published imaging protocol with 2 consecutive 2-dimensional phase-contrast MRI measurements, 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, 7.5◦ ; FOV, 250 × 187.5; 8 averages; slice thickness, 13 mm; velocity sensitivity, 40 cm/s; scan time, 20 seconds) [26].
Image processing Data were analyzed with Matlab (The MathWorks, Natick, Mass, version 7.5) and SPM5 (Wellcome Trust Centre for Neuroimaging, Oxford, UK). CBF (mL·100 mL−1 ·min−1 ) was calculated from the ASL perfusion MR images according to a previously published model [27]. The T2 * of arterial blood and T1 of blood were assumed to be 50 and 1680 ms, respectively [28,29]. The water content of blood was assumed to be 0.76 mL per milliliter of arterial blood [30]. The mean resting magnetization of the blood in all subjects was determined by selecting a region of interest in the cerebrospinal fluid and iteratively fitting the inversion-recovery data according to a previously published procedure [30]. CVR was defined as the percentage of increase in CBF within 15 minutes after administration of acetazolamide. The CBF was therefore calculated at baseline and after the vasodilatory challenge in four regions of interest (ROIs), which were placed cortically in the middle cerebral artery (MCA) territory and subcortically on the head portion of the caudate nucleus, the lentiform nucleus, and the thalamus by a single observer (NSH). For placement of the ROIs a surrogate anatomical T1 -weighted image was calculated from the inversion-recovery sequence by calculating the reciprocal of the quantitative T1 . The ventricular system, anterior limb and posterior limb of the internal capsule, and external capsule were used to delineate the brain structures during the manual segmentation. Areas of hyperintensity on the FLAIR images, indicating areas of infarction, were manually
excluded from the ROIs. The T1 image was further segmented into white and gray matter probability maps with SPM5 software. Thresholding was applied to create a gray matter mask, which was combined with each ROI to avoid partial voluming of white and gray matter. For visualization purposes, the perfusion and reactivity images were spatially smoothed using a Gaussian filter.
Statistical analysis Differences in CBF and CVR values between hemispheres ipsilateral and contralateral to the symptomatic ICA were assessed for each ROI using paired t-tests. A P-value < 0.05 was considered to indicate statistical significance. Since no differences were found in CBF or CVR between the hemispheres in the control group, these values were averaged for further analysis. Increases in CBF measurements before and after administration of acetazolamide were assessed using paired t-tests. Differences in the CBF and CVR measurements between the control group and patient groups were assessed using independent t-tests. A Bonferonni correction was used for multiple comparisons. The corrected P values are reported. Values are expressed as means ± standard error of the mean (SEM) unless otherwise specified. SPSS (SPSS Inc., Chicago, Illinois, version 15) was used for statistical analysis.
Results Table 1 summarizes the demographic and clinical characteristics of the healthy controls and of the patients with an ICA stenosis or occlusion. Perfusion images before and after administration of acetazolamide together with the resulting reactivity images and FLAIR images are shown for a healthy subject (Fig. 1), a patient with an ICA stenosis (Fig. 2), and a patient with an ICA occlusion (Fig. 3). CBF values before and after the vasodilatory challenge and CVR values are summarized for the healthy controls and stenosis and occlusion patients in the regions of the MCA territory, caudate nucleus, lentiform nucleus, and thalamus (Table 2). The baseline CBF in the patients with ICA
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Figure 1 Case example of a 55-year-old healthy subject. Time-of-flight MR angiogram images (A) of the circle of Willis show the presence of all vessels. Images of cerebral perfusion before (B) and after (C) administration of acetazolamide, and of the cerebrovascular reactivity (D) correspond with FLAIR images from cranial (top) to caudal (bottom). The images show the superimposed outline of the regions of interest placed in the middle cerebral artery, caudate nucleus, lentiform nucleus and thalamus. The perfusion images show no evidence of reduced cerebral blood flow. The reactivity images depict the relative increase in cerebral perfusion after administration of acetazolamide.
Figure 2 Case example of a 51-year-old patient with a unilateral symptomatic right ICA stenosis (> 70%). Images (A—E) are depicted identically to Fig. 1. MRA images (A) show the presence of a hypoplastic A1 segment ipsilateral to the stenosis. The cerebral perfusion is reasonably symmetrical between both hemispheres ipsi- and contralateral to the ICA stenosis. The reactivity images however show a subtle deficit in CVR against the right (symptomatic) hemisphere, which is most pronounced subcortically in the left most reactivity image.
stenosis was comparable with that of the healthy controls. In the patients with ICA occlusion the baseline CBF was significantly lower than in the healthy controls for ipsilateral as well as the contralateral hemisphere in the MCA territory (P = 0.012, and P = 0.036 respectively), caudate nucleus (P < 0.001, and P = 0.012 respectively), and thalamus (P < 0.001, and P = 0.012 respectively). When compared to controls, the CVR in patients with ICA stenosis was significantly lower in the caudate (P = 0.006) and lentiform nucleus (P < 0.036) ipsilateral to the stenosis.
In the patients with ICA stenosis, the CVR in the caudate nucleus contralateral to the stenosis was significantly lower (P = 0.006) as well. In patients with ICA occlusion, the CVR in the hemisphere ipsilateral to the occlusion as well as in the contralateral hemisphere was significantly lower in the MCA territory (both sides P < 0.001), the caudate (both sides P < 0.001) and lentiform nucleus (both sides P < 0.001), and in the thalamus (P = 0.048, and P = 0.006 respectively). In the patients, no significant differences in CVR were found between hemispheres ipsilateral to the ICA occlusion or
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Cerebrovascular reactivity in the basal ganglia of patients with carotid artery disease
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Figure 3 Case example of a 50-year-old patient with a unilateral symptomatic right ICA occlusion. Images (A—E) are depicted identically to Fig. 1. The cerebral perfusion is asymmetrical between both hemispheres ipsi- and contralateral to the ICA occlusion. The reactivity images demonstrate severely reduced CVR in the right (symptomatic) hemisphere as well as decreased CVR in the left (asymptomatic) hemisphere.
Table 2
Cerebral blood flow and reactivity after administration of acetazolamide.
Region and group
Hemisphere
CBF (mL·100 mL−1 ·min−1 ) Pre-ACZ
MCA territory Healthy controls Stenosis patients Occlusion patients Caudate nucleus Healthy controls Stenosis patients Occlusion patients Lentiform nucleus Healthy controls Stenosis patients Occlusion patients Thalamus Healthy controls Stenosis patients Occlusion patients
Reactivity (%)
Post-ACZ
Both Stenosed side Contralateral side Occluded side Contralateral side
45.2 43.8 45.0 37.8 41.7
± ± ± ± ±
1.3 1.3 1.7 3.0* 1.4*
67.0 60.4 62.8 43.5 50.8
± ± ± ± ±
1.8 2.6 2.4 3.6 2.4
48.8 37.9 40.5 15.8 22.5
± ± ± ± ±
2.1 4.4 3.5 4.0*,† 4.5*,†
Both Stenosed side Contralateral side Occluded side Contralateral side
36.2 37.9 38.0 27.1 31.3
± ± ± ± ±
1.1 2.5 1.9 2.3*,† 1.7*,†
55.4 48.9 50.5 31.3 36.8
± ± ± ± ±
1.5 3.0 2.5 3.1 2.3
54.2 29.9 34.4 13.9 17.6
± ± ± ± ±
2.9 6.6* 4.5* 5.0* 4.0*,†
Both Stenosed side Contralateral side Occluded side Contralateral side
35.9 38.1 36.0 31.8 33.3
± ± ± ± ±
1.1 3.1 1.7 2.8* 1.1*
51.6 47.7 48.3 36.7 39.5
± ± ± ± ±
1.6 2.3 2.1 3.3 1.9
44.3 30.2 35.6 16.3 18.3
± ± ± ± ±
2.0 4.7* 4.1 4.1* 3.8*,†
Both Stenosed side Contralateral side Occluded side Contralateral side
48.9 44.8 48.2 37.8 41.4
± ± ± ± ±
2.1 2.9 2.6 2.1* 1.9*
79.3 70.5 75.9 54.6 59.4
± ± ± ± ±
3.0 4.0 3.3 3.3 3.1
64.4 60.7 60.2 46.1 43.8
± ± ± ± ±
3.8 5.3 4.7 6.1* 4.5*
Cerebral blood flow (CBF) before (pre-ACZ) and after (post-ACZ) administration of acetazolamide with reactivity per region of interest, patient group and hemisphere. * Significant difference between patients and healthy controls (P < 0.05). † Significant difference between symptomatic stenosis patients and occlusion patients (P < 0.05).
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N.S. Hartkamp et al. Table 3
Summary of the circle of Willis’ variations in the study population.
Anterior circulation Missing Acom or A1 segment Anterior collateral flow Posterior circulation Ipsilateral fetal type PCA Posterior-to-anterior collateral flow Vertebrobasilar system < 50% stenosis in one vertebral artery
Healthy controls
Stenosis patients
Occlusions patients
0 0
0 4
0 6
0 0
1 0
0 4
0
3
1
stenosis and the contralateral hemisphere. In patients with an ICA occlusion, the CVR was significantly lower than in stenosis patients in the MCA territory in both the ipsilateral (P = 0.006) as contralateral hemisphere (P = 0.018). The CVR in patients with an ICA occlusion was also significantly lower than in stenosis patients for the caudate (P = 0.048) and lentiform nucleus (P = 0.024) of the contralateral hemisphere.
Collateral circulation and morphology of the circle of Willis Circle of Willis’ variations are summarized in Table 3. Regarding the anterior collateral circulation in the circle of Willis there were no subjects with a missing anterior communicating artery or a missing pre-communicating segment (A1 segment) of the anterior cerebral artery. A retrograde flow in the ipsilateral A1 segment was found on phase-contrast MR angiography, indicating anterior collateral flow in the circle of Willis in four patients with an ICA stenosis and six patients with an ICA occlusion. No significant difference was found in reactivity of either hemisphere between patients with and patients without confirmed anterior collateral blood flow. Regarding the posterior collateral circulation in the circle of Willis there was one patient with an ICA stenosis found to have a missing pre-communicating segment (P1 segment) of the ipsilateral posterior cerebral artery. Four patients with an ICA occlusion had retrograde flow in the ipsilateral posterior communicating artery as found on phase-contrast MR angiography. In none of the patients with ICA stenosis retrograde flow was found in the posterior communicating artery. No significant difference was found in reactivity of either hemisphere between patients with and without confirmed posterior collateral blood flow. Regarding the vertebrobasilar circulation a < 50% stenosis of one of the vertebral arteries was present in three patients with an ICA stenosis and one patient with an ICA occlusion. In all patients an antegrade flow was found on duplex echography in the vertebrobasilar system.
Discussion In the present study, we were able to assess the hemodynamic status in the MCA territory as well as in the basal ganglia of patients with atherosclerotic steno-occlusive disease of the internal carotid artery. Atherosclerosis is a generalized disease and it is very likely that vascular
risk factors affect both the large and the small arteries. Recently, it has been suggested however that subcortical endothelial dysfunction is not only specific to small vessel disease [31]. Our findings illustrate that hemodynamic impairment distal to a carotid artery stenosis or occlusion is most likely also accompanied with hemodynamic compromise in the subcortical gray matter such as the basal ganglia. Our results are comparable with those of other studies that have investigated CBF at baseline and CVR in the basal ganglia at the brain tissue level using SPECT [32], PET [33] or ASL MRI [18,19] in healthy subjects. However, none of these studies have investigated patients with steno-occlusive carotid artery disease. In the current study population no brain tissue damage such as lacunar infarcts was present subcortically. The impaired CVR suggests though that the basal ganglia may be vulnerable to hemodynamic stroke due to ICA stenosis or occlusion. The CVR in the thalamus of the patients with ICA occlusion was also reduced compared to healthy controls. The CVR in patients with ICA stenosis was impaired in the caudate nucleus of the hemisphere contralateral to the stenosis and in patients with ICA occlusion the CVR in the contralateral hemisphere was impaired in the MCA territory, caudate and lentiform nucleus, and thalamus as well. The hemodynamic impairment in the contralateral hemisphere may indicate that the cerebral vascular compensation mechanism, such as vasodilatation of resistance arterioles, is also affected in the vasculature of the hemisphere contralateral to the carotid artery with steno-occlusive disease. A previous study showed higher prevalence of infarcts and white matter lesions in patients with ICA occlusion both ipsilateral as well as contralateral to the occlusion [34]. This is in line with the current suggestion of a more globally impaired hemodynamic status of the brain due to a unilateral ICA occlusion or stenosis. Presence of collateral flow via the circle of Willis might potentially also influence the reactivity of the contralateral hemisphere, although we did not found significant differences in the current study. Alternatively, generalized atherosclerosis in patients with carotid artery stenosis or occlusion may affect also the CVR of the contralateral hemisphere and posterior circulation in patients with carotid artery stenosis or occlusion. The employed ASL MR imaging technique has inherent limitations such as reduced sensitivity for delayed perfusion and blood flow velocity dependent labeling efficiency. To overcome underestimation of perfusion via collateral pathways, we used pseudo-continuous ASL labeling technique
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Cerebrovascular reactivity in the basal ganglia of patients with carotid artery disease with an effective delay time of more than 3 seconds. This delay allows the magnetically labeled blood to reach the brain tissue in patients with steno-occlusive carotid artery disease [35]. As a result of administration of acetazolamide, the blood flow increases which leads to reduced labeling efficiency and an underestimation of CBF and CVR. This effect will however be present in the healthy controls as well as in the patients with an ICA stenosis or occlusion. Another limitation is the partial volumes of grey matter and white matter within any voxel. The lower white matter ASL signal dilutes the grey matter ASL signal. To account for this, a grey matter mask was used to select voxels with maximum grey matter content. The lower amount of remaining available voxels for each ROI is reflected in the spread of the data. In the current study we did not determine the stroke etiology or investigate whether our imaging findings could potentially help establish the etiological classification. Nevertheless, CVR measurements at brain tissue level with ASL MRI can provide valuable information regarding the hemodynamic status of the basal ganglia and gray matter, and warrants further investigation in a longitudinal setting to determine if can influence the determination of stroke etiology and clinical treatment.
Conclusion Perfusion ASL MR imaging can quantitatively assess the cerebral hemodynamic autoregulation of the basal ganglia in patients with steno-occlusive carotid artery disease. Our results show that, in patients with steno-occlusive disease of the internal carotid arteries the hemodynamic autoregulation in the basal ganglia is globally impaired.
Grant support J. Hendrikse receives support from the Dutch Heart Foundation (Grant 2010B274) and European Research Council (ERC-2014-STG-637024). R.P.H. Bokkers receives support from the Dutch Heart Foundation (Grant 2013T047).
Disclosure of interest The authors declare that they have no competing interest.
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Please cite this article in press as: Hartkamp NS, et al. Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease. J Neuroradiol (2016), http://dx.doi.org/10.1016/j.neurad.2016.07.003