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Relationship between the hemodynamic changes on multi-Td pulsed arterial spin labeling images and the degrees of cerebral artery stenosis
Magnetic Resonance Imaging 32 (2014) 1277–1283
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Magnetic Resonance Imaging journal homepage: www.mrijournal.com
Relationship between the hemodynamic changes on multi-Td pulsed arterial spin labeling images and the degrees of cerebral artery stenosis Jun Chen a, b, Bin Zhao a,⁎, Chunqing Bu b, Guohua Xie b a b
Shandong Medical Imaging Research Institute, Shandong University, Jinan, Jingwu Road No.324, Jinan 250021, Shandong province, China Department of Radiology, Liaocheng City People's Hospital, Dongchang West Road No.67, Liaocheng 252000, Shandong Province, China
a r t i c l e
i n f o
Article history: Received 9 January 2014 Revised 11 July 2014 Accepted 18 August 2014 Keywords: Hemodynamic change Multi-Td PASL Cerebral artery stenosis
a b s t r a c t Objective: To explore the relationship between the hemodynamic changes on multi-Td (delay time) pulsed arterial spin labeling (PASL) images and the degrees of cerebral artery stenosis, and to evaluate the value of multi-Td PASL in detecting the signal changes in cerebral arteries with stenosis. Patients and methods: 29 patients with less than 50% stenosis (mild stenosis group) and 22 patients with 50%–69% stenosis (moderate stenosis group) in M1 segment of unilateral middle cerebral artery (MCA) were included in this study. The degrees of MCA stenosis were measured using time of flight MR angiography (TOF MRA). Multi-Td PASL imaging was performed to detect the signal changes in bilateral MCA. We selected and hand-drew bilateral symmetric branches of MCA as regions of interest (ROIs) on eight-Td PASL images. The intensities of ROIs were measured, and the time-signal intensity curves were acquired by post-processing on a MR workstation. SPSS19.0 statistical software was used for statistics. The differences in the peak intensities and the times to peak intensities between the normal and narrowed sides of the mild and moderate stenosis groups were respectively examined by paired-samples t test. The differences in the changes of peak intensities and times to peak intensity of the two sides between the mild and moderate stenosis groups were examined by independent samples t test. A p value less than 0.05 was considered statistically significant. Result: There were significant difference in the peak intensities (t = −2.720, p = 0.011 b 0.05) and no significant difference in the times to peak intensities (t = −1.279, p = 0.212 N 0.05) between the normal and narrowed sides of the mild stenosis group. There were both significant differences in the peak intensities (t = −6.076, p = 0.000 b 0.05) and times to peak intensities (t = 7.232, p = 0.000 b 0.05) between the normal side and narrowed side of the moderate stenosis group. There were both significant differences in the changes of peak intensities (t = −2.11, p = 0.040 b 0.05) and times to peak intensity (t = −4.23, p = 0.000 b 0.05) between the mild and moderate stenosis groups. Conclusion: The hemodynamic changes on multi-Td PASL images were different with the degrees of cerebral artery stenosis. Moderate stenosis means greater hemodynamic changes in the arteries than mild stenosis. MultiTd PASL imaging is a promising means to evaluate the hemodynamic changes in cerebral arteries with stenosis. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Cerebral artery stenosis is a common etiology for ischemic cerebrovascular disease. The rate of stroke ipsilateral to the cerebral artery stenosis is 11% at 1 year and 14% at 2 years despite the use of either warfarin or aspirin and vascular risk factor modification [1]. Ischemic cerebrovascular diseases frequently manifest themselves first as hemodynamic changes before cerebral infarction can be observed. These hemodynamic changes are important indicators of the physiological status of the brain. ⁎ Corresponding author. E-mail address: [email protected] (B. Zhao). http://dx.doi.org/10.1016/j.mri.2014.08.017 0730-725X/© 2014 Elsevier Inc. All rights reserved.
Digital subtraction angiography (DSA) is the gold standard for detecting cerebral artery stenosis [2], but it needs contrast agent injection. Time of flight MR angiography (TOF MRA) has been a common means of imaging cerebral arteries with the development of high field strength MR. Some studies have proven that TOF MRA using high field MR has high sensitivity and specificity in detecting cerebral artery stenosis [3]. Cerebral blood flow can be measured by perfusion imaging, such as positron emission tomography (PET) [4], single photon emission computed tomography (SPECT) [5] and CT perfusion imaging [6], but these techniques need injection of exogenous contrast agent. MR provides two different approaches to measure cerebral perfusion: dynamic susceptibility contrast (DSC) [7] and arterial spin labeling
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(ASL) perfusion imaging techniques. DSC perfusion imaging technique can measure relative cerebral perfusion parameters, including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP). Due to more realizations of the side effects of MR contrast agent such as the development of nephrogenic systemic fibrosis (NSF) [8], the use of MR contrast agent has become discreet. ASL does not require injection of contrast agent, which is completely none-invasive and acceptable to patients. Compared with DSC technique, ASL has its own unique advantage. A study showed ASL technique could provide additional and complementary hemodynamic abnormalities in about half of the patients with normal DSC perfusion imaging findings [9]. ASL uses magnetically labeled water protons in arterial blood as the endogenous tracer. Blood proximal to the brain are inverted using radio frequency. When labeled tracer reaches the imaging slices, it gives rise to perfusion signal in the slices. Multi-Td PASL imaging technique is used to detect these signal changes [10]. ASL has been applied in quantification of the CBF [11] and identification of the presence and intensity of collateral perfusion in patients with moyamoya disease [7]. The most common location for ischemic stroke is in the middle cerebral artery (MCA) territory [12]. The majority of the primary motor and somatosensory cortices are supplied by MCA. When MCA is narrowed, the blood supply from MCA is restricted. The understanding of the hemodynamic changes may help provide a basis for clinical treatment of ischemic cerebrovascular disease, but the degrees of MCA stenosis which can obviously affect the hemodynamic changes in arteries are not determined. The goal of this study was to explore the relationship between the hemodynamic changes on multi-Td PASL images and the degrees of cerebral artery stenosis, and to evaluate the value of multi-Td PASL to detect the signal changes in cerebral arteries with stenosis. 2. Material and methods This study was approved by the institutional review board at our institution. Written informed consents were obtained from all patients. 2.1. Study population Between September 2012 and June 2013, 29 patients (17 males and 12 females, aged 43–82 years with a mean age of 59 years) with less 50% stenosis (mild stenosis group) and 22 patients (8 males and 14 females, aged 45–77 years with a mean age of 55 years) with 50% ~ 69% stenosis (moderate stenosis group) in M1segment of unilateral MCA were included in this study. All patients had ischemic cerebrovascular symptom, such as sensory loss of the unilateral face, speech impairments, hemiparesis, et al. The degrees of the arterial stenosis were measured using TOF MRA according to a study of Samuels OB and his colleagues [13]. 2.2. MRI protocol All MR examinations were performed on an Achieva 3 Tesla MR scanner (Philips Medical Systems, Netherlands) using a 16-channel phased-array neurovascular coil. All patients underwent intracranial TOF MRA with the following parameters [14]: three-dimensional (3D) fast field echo (FFE), TR/TE = 20 ms/3.5 ms, flip angle = 18°, slices = 160, voxel size = 0.6 × 0.6 × 1 mm3, FOV = 220 mm × 220 mm and NSA = 2. Multi-Td PASL imaging were performed using a STAR (signal targeting by alternating radiofrequency pulses) labeling technique with the following parameters [10]: single-shot FFE planar imaging (EPI), TE = 16 ms, flip angle = 40°, matrix size = 64 × 64, voxel
size = 3.48 × 3.48 mm 2 , FOV = 240 × 240 mm 2 , slice thickness = 6 mm, sensitivity encoding factor = 2.3, label thickness = 130 mm, number of slices = 6, staring Td = 300 ms, Td interval = 250 ms and 8-Td images acquired. Two acquisitions are carried out: one with the labeled water protons and a control acquisition without arterial labeling. 30 dynamic scans were used. 2.3. Image evaluation The multi-Td PASL images were obtained by averaging the subtraction of the control and labeled acquisitions on a post-processing station (Extended MR Workstation; Philips Medical Systems). We selected and hand-drew bilateral symmetric branches of MCA as regions of interest (ROIs) on 8-Td PASL images. The intensities of ROIs were measured, and the time-signal intensity (TIC) curves were calculated by post-processing on the MR workstation as seen on Figs. 2, 3, 5 and 6. X-axis of TIC stands for delay time, and y-axis stands for signal intensity of ROIs [10]. The t = 0 point is the time of labeling. The peak intensity and time to peak intensity of each ROI could be observed on the TIC images. We also examined the changes of the peak intensities (peak intensity of normal side-peak intensity of narrowed side) and the changes of times to peak intensity (time to peak intensity of narrowed side-time to peak intensity of normal side) of the mild and moderate stenosis groups. 2.4. Statistical analysis The peak intensities and times to peak intensities were present as means ± standard deviation (SD). SPSS19.0 statistical software was used for statistics. The differences in the peak intensities and time to peak intensities between the normal side and narrowed sides of the mild and moderate stenosis groups were respectively examined by paired-sample t test. The differences in the changes of peak intensities and times to peak intensity on two sides between the mild and moderate stenosis groups were examined by independent samples t test. A p value less than 0.05 was considered statistically significant. 3. Results We measure the degrees of the stenosis in M1 segment of MCA on TOF MRA images. Figs. 1–3. A 47-year-old man. Mild stenosis in M1 segment of right MCA (arrow) was seen on TOF MRA (Fig. 1). The time intensity curves of left and right ROIs were seen on Figs. 2 and 3, respectively. The intensities and times to peak intensities of left and right ROIs were respectively 127.5, 927 ms and 122.3, 927 ms. Figs. 4–6. A 74-year-old woman. Moderate stenosis in M1 segment of right MCA (arrow) was seen on TOF MRA (Fig. 4). The time intensity curves of left and right ROIs were seen on Figs. 5 and 6, respectively. The peak intensities and times to peak intensities of left and right ROIs were respectively 88.2, 1209 ms and 84.6, 1459 ms. The peak intensities in ROIs on the normal and narrowed sides of mild stenosis group were 110.8 ± 9.39, 106.76 ± 11.92 (mean ± SD), respectively. The times to peak intensities of ROIs on normal and narrowed sides of mild stenosis group were 1037.28 ± 126.09 and 1071.76 ± 129.85, respectively. There were significant difference in the peak intensities (t = − 2.720, p = 0.011 b 0.05) and no significant difference in the times to peak intensities (t = − 1.279, p = 0.212 N 0.05) between normal and narrowed sides in mild stenosis group (Table 1). The peak intensities in ROIs on normal and narrowed sides of moderate stenosis group were 106.90 ± 11.46 and 98.77 ± 12.21, respectively. The times to peak intensities in ROIs on normal and narrowed sides of moderate stenosis group were 1021.09 ± 119.72 and 1237.09 ± 167.45, respectively. There were both significant
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difference in the peak intensities (t = −6.076, p = 0.000 b 0.05) and the times to peak intensities (t = 7.232, p = 0.000 b 0.05) between the normal and narrowed sides in moderate stenosis group (Table 2). The changes of peak intensities of mild and moderate stenosis groups were 3.30 ± 7.93 and 8.10 ± 6.54, respectively. The changes of times to peak intensities of mild and moderate stenosis groups were 34.48 ± 145.22 and 215.90 ± 159.90, respectively. There were both significant difference in the changes of peak intensities (t = − 2.11, p = 0.040 b 0.05) and times to peak intensities (t = − 4.23, p = 0.000 b 0.05) between mild and moderate stenosis group (Table 3).
4. Discussion
Fig. 1. A 47-year-old man with mild stenosis in M1 segment of right MCA. TOF MRA.
ASL techniques can be categorized into PASL, continuous ASL (CASL) and pseudo-continuous ASL (PCASL). The intrinsically low SNR of ASL has limited its application. Although CASL techniques have higher signal-to-noise ratio (SNR), they have been limited in
Fig. 2. A 47-year-old man with mild stenosis in M1 segment of right MCA. The PASL images and TIC curve of left ROIs.
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Fig. 3. A 47-year-old man with mild stenosis in M1 segment of right MCA. The PASL images and TIC curve of right ROIs.
Fig. 4. A 74-year-old woman with moderate stenosis in M1 segment of right MCA. TOF MRA.
clinical practice by high radiofrequency energy deposition and more demanding requirements from the scanner's hardware [15]. For most PASL techniques, the tagging efficiency is greater than 95% [16]. PCASL has been introduced as an intermediate means to take advantage of CASL's high SNR and PASL's high tagging efficiency. In recent years, the ease of implementation has made PASL a frequent use for neuroimaging [17,18]. The duration for the labeled tracer to travel from the labeling region to the imaging slices is known as arterial transit time (ATT). PASL is sensitive to ATT, which can either lead to over-estimation of CBF due to bright intravascular spins or under-estimation of CBF due to delayed arrival [19]. The display of dynamic signal changes can reduce these mistakes. High temporal resolution and SNR are needed to detect these signal changes in the arteries in this study. Great tagging efficiency can raise the signal intensities in the arteries and contribute to the improvement of SNR of the PASL images. Methods for improving temporal resolution include single-shot ASL [20], because the center of kspace is acquired during each acquisition. Multi-Td PASL imaging has the ability to improve temporal resolution using single-shot technique [10].
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Fig. 5. A 74-year-old woman with moderate stenosis in M1 segment of right MCA. The PASL images and TIC curve of left ROIs.
The ischemic symptoms in patients with cerebral artery stenosis can be caused by atheromatous thrombosis, embolic disease, vasculitis or vasospasm [21]. The hemodynamic changes in the arteries are correlated with the degrees of arterial stenosis. The results of our study showed that there were significant difference in the peak intensities and no significant difference in the times to peak intensities between normal and narrowed sides in mild stenosis group. Blood supply from MCA with mild stenosis were not delayed, but only decreased. There were both significant difference in the peak intensities and the times to peak intensities between normal and narrowed sides in moderate stenosis group. Blood supply from MCA with moderate stenosis were delayed and also decreased. The hemodynamic signal changes on multi-Td PASL images represent the changes of blood supply from narrowed arteries. We also found that there were both significant differences in the changes of peak intensities and times to peak intensities between mild and moderate stenosis groups. Moderate stenosis means greater hemodynamic changes in the arteries than mild stenosis. There was a limitation that patients with sever stenosis of MCA were not included in this study. The label interval and circle duration of multi-Td PASL sequence used in this study were 300 ms and
2000 ms, respectively. Blood flow was very slow when MCA were severely narrowed, so the peak signals in branches of MCA were out of acquisition. The prolongation of the delay times may be useful to detect the signal changes in cerebral arteries with sever stenosis. In conclusion, the hemodynamic changes were different with the degrees of cerebral artery stenosis. Moderate stenosis means greater dynamic changes in the arteries than mild stenosis. Multi-Td PASL imaging is a promising mean to demonstrate the hemodynamic changes of cerebral arteries with stenosis. The blood supply of brain from narrowed cerebral artery can be well displayed, which can provide useful information for clinical treatment.
References [1] Kasner SE, Chimowitz MI, Lynn MJ, et al. Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis. Circulation 2006;113: 555–63. [2] Duffis EJ, Jethwa P, Gupta G, et al. Accuracy of computed tomographic angiography compared to digital subtraction angiography in the diagnosis of intracranial stenosis and its impact on clinical decision-making. J Stroke Cerebrovasc Dis 2013;22:1013–7.
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Fig. 6. A 74-year-old woman with moderate stenosis in M1 segment of right MCA. The PASL images and TIC curve of right ROIs. Table 1 The peak intensities and times to peak intensities of mild stenosis group.
Peak intensities Times to peak intensities
Normal side
Narrowed side
t value
p value
110.8 ± 9.39 1037.28 ± 126.09
106.76 ± 11.92 1071.76 ± 129.85
−2.720 1.279
0.011 0.212
Table 2 The peak intensities and times to peak intensities of moderate stenosis group.
Peak intensities Times to peak intensities
Normal side
Narrowed side
t value
p value
106.90 ± 11.46 1021.09 ± 119.72
98.77 ± 12.21 1237.09 ± 167.45
−6.076 7.232
0.000 0.000
Table 3 The changes of peak intensities and times to peak intensities. Mild stenosis group
Moderate stenosis group
t value p value
Peak intensities 3.30 ± 7.93 8.10 ± 6.54 −2.11 Times to peak intensities 34.48 ± 145.22 215.90 ± 159.90 −4.23
0.040 0.000
[3] Choi CG, Lee DH, Lee JH, et al. Detection of intracranial atherosclerotic stenoocclusive disease with 3D time-of-flight magnetic resonance angiography with sensitivity encoding at 3 T. Am J Neuroradiol 2007;28:439–46. [4] Mintun MA, Raichle ME, Martin WR, Herscovitch P. Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography. J Nucl Med 1984;25(2):177–87. [5] Devous Sr MD, Stokely EM, Chehabi HH, Bonte FJ. Normal distribution of regional cerebral blood flow measured by dynamic single-photon emission tomography. J Cereb Blood Flow Metab 1986;6(1):95–104. [6] Rai AT, Carpenter JS, Peykanu JA, et al. The role of CT perfusion imaging in acute stroke diagnosis: a large single-center experience. J Emerg Med 2008;35: 287–92. [7] Wang DJ, Alger JR, Qiao JX, et al. The value of arterial spin-labeled perfusion imaging in acute ischemic stroke: comparison with dynamic susceptibility contrast-enhanced MRI. Stroke 2012;43:1018–24. [8] Thomsen HS, Morcos SK, Dawson P, et al. Is there a causal relation between the administration of gadolinium based contrast media and the development of nephrogenic systemic fibrosis (NSF). Clin Radiol 2006;61:905–6. [9] Zaharchuk G, Bammer R, Straka M, et al. Arterial spin-label imaging in patients with normal bolus perfusion-weighted MR imaging findings: pilot identification of the borderzone sign. Radiology 2009;252:797–807. [10] Fonda C, Ciccarone A, Mortilla M, et al. 3 T arterial spin labeling (ASL) in pediatric patients: preliminary results. 6th congress and exhibition of the joint societies of paediatric radiology. London: Elsevier; 2011. [11] Petersen ET, Zimine I, Ho YC, et al. Non-invasive measurement of perfusion: a critical review of arterial spin labeling techniques. Br J Radiol 2006;79: 688–701. [12] O'Sullivan Susan. Phys Rehabil 2007:711–2 [ISBN 0-8036-1247-8].
J. Chen et al. / Magnetic Resonance Imaging 32 (2014) 1277–1283 [13] Samuels OB, Joseph GJ, Lynn MJ. A standardized method for measuring intracranial arterial stenosis. Am J Neuroradiol 2000;21:643–6. [14] Jun C, Yujin D, Yanfeng Z, et al. The combined application of multi-technology at 3.0 T MR in detecting stenosis of head and neck arteries. J Med Imaging 2010;20: 321–4. [15] Detre JA, Alsop DC. Perfusion magnetic resonance imaging with continuous arterial spin labeling: methods and clinical applications in the central nervous system. Eur J Radiol 1999;30:115–24. [16] Wong EC. Quantifying CBF, with pulsed ASL: technical and pulse sequence factors. J Magn Reson Imaging 2005;22:727–31.
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[17] Petcharunpaisan S, Ramalho J, Castillo M. Arterial spin labeling in neuroimaging. World J Radiol 2010;10:384–98. [18] Gregori J, Schuff N, Kern R, et al. T2-based arterial spin labeling measurements of blood to tissue water transfer in human brain. J Magn Reson Imaging 2013;37:332–42. [19] Golay X, Hendrikse J, Lim TC. Perfusion imaging using arterial spin labeling. Top Magn Reson Imaging 2004;15:10–27. [20] Petcharunpaisan S, Ramalho J, Castillo M. Arterial spin labeling in neuroimaging. World J Radiol 2010;2:384–98. [21] Watts JM, Whitlow CT, Maldjian JA. Clinical applications of arterial spin labeling. NMR Biomed 2013;26:892–900.
Contents lists available at ScienceDirect
Magnetic Resonance Imaging journal homepage: www.mrijournal.com
Relationship between the hemodynamic changes on multi-Td pulsed arterial spin labeling images and the degrees of cerebral artery stenosis Jun Chen a, b, Bin Zhao a,⁎, Chunqing Bu b, Guohua Xie b a b
Shandong Medical Imaging Research Institute, Shandong University, Jinan, Jingwu Road No.324, Jinan 250021, Shandong province, China Department of Radiology, Liaocheng City People's Hospital, Dongchang West Road No.67, Liaocheng 252000, Shandong Province, China
a r t i c l e
i n f o
Article history: Received 9 January 2014 Revised 11 July 2014 Accepted 18 August 2014 Keywords: Hemodynamic change Multi-Td PASL Cerebral artery stenosis
a b s t r a c t Objective: To explore the relationship between the hemodynamic changes on multi-Td (delay time) pulsed arterial spin labeling (PASL) images and the degrees of cerebral artery stenosis, and to evaluate the value of multi-Td PASL in detecting the signal changes in cerebral arteries with stenosis. Patients and methods: 29 patients with less than 50% stenosis (mild stenosis group) and 22 patients with 50%–69% stenosis (moderate stenosis group) in M1 segment of unilateral middle cerebral artery (MCA) were included in this study. The degrees of MCA stenosis were measured using time of flight MR angiography (TOF MRA). Multi-Td PASL imaging was performed to detect the signal changes in bilateral MCA. We selected and hand-drew bilateral symmetric branches of MCA as regions of interest (ROIs) on eight-Td PASL images. The intensities of ROIs were measured, and the time-signal intensity curves were acquired by post-processing on a MR workstation. SPSS19.0 statistical software was used for statistics. The differences in the peak intensities and the times to peak intensities between the normal and narrowed sides of the mild and moderate stenosis groups were respectively examined by paired-samples t test. The differences in the changes of peak intensities and times to peak intensity of the two sides between the mild and moderate stenosis groups were examined by independent samples t test. A p value less than 0.05 was considered statistically significant. Result: There were significant difference in the peak intensities (t = −2.720, p = 0.011 b 0.05) and no significant difference in the times to peak intensities (t = −1.279, p = 0.212 N 0.05) between the normal and narrowed sides of the mild stenosis group. There were both significant differences in the peak intensities (t = −6.076, p = 0.000 b 0.05) and times to peak intensities (t = 7.232, p = 0.000 b 0.05) between the normal side and narrowed side of the moderate stenosis group. There were both significant differences in the changes of peak intensities (t = −2.11, p = 0.040 b 0.05) and times to peak intensity (t = −4.23, p = 0.000 b 0.05) between the mild and moderate stenosis groups. Conclusion: The hemodynamic changes on multi-Td PASL images were different with the degrees of cerebral artery stenosis. Moderate stenosis means greater hemodynamic changes in the arteries than mild stenosis. MultiTd PASL imaging is a promising means to evaluate the hemodynamic changes in cerebral arteries with stenosis. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Cerebral artery stenosis is a common etiology for ischemic cerebrovascular disease. The rate of stroke ipsilateral to the cerebral artery stenosis is 11% at 1 year and 14% at 2 years despite the use of either warfarin or aspirin and vascular risk factor modification [1]. Ischemic cerebrovascular diseases frequently manifest themselves first as hemodynamic changes before cerebral infarction can be observed. These hemodynamic changes are important indicators of the physiological status of the brain. ⁎ Corresponding author. E-mail address: [email protected] (B. Zhao). http://dx.doi.org/10.1016/j.mri.2014.08.017 0730-725X/© 2014 Elsevier Inc. All rights reserved.
Digital subtraction angiography (DSA) is the gold standard for detecting cerebral artery stenosis [2], but it needs contrast agent injection. Time of flight MR angiography (TOF MRA) has been a common means of imaging cerebral arteries with the development of high field strength MR. Some studies have proven that TOF MRA using high field MR has high sensitivity and specificity in detecting cerebral artery stenosis [3]. Cerebral blood flow can be measured by perfusion imaging, such as positron emission tomography (PET) [4], single photon emission computed tomography (SPECT) [5] and CT perfusion imaging [6], but these techniques need injection of exogenous contrast agent. MR provides two different approaches to measure cerebral perfusion: dynamic susceptibility contrast (DSC) [7] and arterial spin labeling
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(ASL) perfusion imaging techniques. DSC perfusion imaging technique can measure relative cerebral perfusion parameters, including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP). Due to more realizations of the side effects of MR contrast agent such as the development of nephrogenic systemic fibrosis (NSF) [8], the use of MR contrast agent has become discreet. ASL does not require injection of contrast agent, which is completely none-invasive and acceptable to patients. Compared with DSC technique, ASL has its own unique advantage. A study showed ASL technique could provide additional and complementary hemodynamic abnormalities in about half of the patients with normal DSC perfusion imaging findings [9]. ASL uses magnetically labeled water protons in arterial blood as the endogenous tracer. Blood proximal to the brain are inverted using radio frequency. When labeled tracer reaches the imaging slices, it gives rise to perfusion signal in the slices. Multi-Td PASL imaging technique is used to detect these signal changes [10]. ASL has been applied in quantification of the CBF [11] and identification of the presence and intensity of collateral perfusion in patients with moyamoya disease [7]. The most common location for ischemic stroke is in the middle cerebral artery (MCA) territory [12]. The majority of the primary motor and somatosensory cortices are supplied by MCA. When MCA is narrowed, the blood supply from MCA is restricted. The understanding of the hemodynamic changes may help provide a basis for clinical treatment of ischemic cerebrovascular disease, but the degrees of MCA stenosis which can obviously affect the hemodynamic changes in arteries are not determined. The goal of this study was to explore the relationship between the hemodynamic changes on multi-Td PASL images and the degrees of cerebral artery stenosis, and to evaluate the value of multi-Td PASL to detect the signal changes in cerebral arteries with stenosis. 2. Material and methods This study was approved by the institutional review board at our institution. Written informed consents were obtained from all patients. 2.1. Study population Between September 2012 and June 2013, 29 patients (17 males and 12 females, aged 43–82 years with a mean age of 59 years) with less 50% stenosis (mild stenosis group) and 22 patients (8 males and 14 females, aged 45–77 years with a mean age of 55 years) with 50% ~ 69% stenosis (moderate stenosis group) in M1segment of unilateral MCA were included in this study. All patients had ischemic cerebrovascular symptom, such as sensory loss of the unilateral face, speech impairments, hemiparesis, et al. The degrees of the arterial stenosis were measured using TOF MRA according to a study of Samuels OB and his colleagues [13]. 2.2. MRI protocol All MR examinations were performed on an Achieva 3 Tesla MR scanner (Philips Medical Systems, Netherlands) using a 16-channel phased-array neurovascular coil. All patients underwent intracranial TOF MRA with the following parameters [14]: three-dimensional (3D) fast field echo (FFE), TR/TE = 20 ms/3.5 ms, flip angle = 18°, slices = 160, voxel size = 0.6 × 0.6 × 1 mm3, FOV = 220 mm × 220 mm and NSA = 2. Multi-Td PASL imaging were performed using a STAR (signal targeting by alternating radiofrequency pulses) labeling technique with the following parameters [10]: single-shot FFE planar imaging (EPI), TE = 16 ms, flip angle = 40°, matrix size = 64 × 64, voxel
size = 3.48 × 3.48 mm 2 , FOV = 240 × 240 mm 2 , slice thickness = 6 mm, sensitivity encoding factor = 2.3, label thickness = 130 mm, number of slices = 6, staring Td = 300 ms, Td interval = 250 ms and 8-Td images acquired. Two acquisitions are carried out: one with the labeled water protons and a control acquisition without arterial labeling. 30 dynamic scans were used. 2.3. Image evaluation The multi-Td PASL images were obtained by averaging the subtraction of the control and labeled acquisitions on a post-processing station (Extended MR Workstation; Philips Medical Systems). We selected and hand-drew bilateral symmetric branches of MCA as regions of interest (ROIs) on 8-Td PASL images. The intensities of ROIs were measured, and the time-signal intensity (TIC) curves were calculated by post-processing on the MR workstation as seen on Figs. 2, 3, 5 and 6. X-axis of TIC stands for delay time, and y-axis stands for signal intensity of ROIs [10]. The t = 0 point is the time of labeling. The peak intensity and time to peak intensity of each ROI could be observed on the TIC images. We also examined the changes of the peak intensities (peak intensity of normal side-peak intensity of narrowed side) and the changes of times to peak intensity (time to peak intensity of narrowed side-time to peak intensity of normal side) of the mild and moderate stenosis groups. 2.4. Statistical analysis The peak intensities and times to peak intensities were present as means ± standard deviation (SD). SPSS19.0 statistical software was used for statistics. The differences in the peak intensities and time to peak intensities between the normal side and narrowed sides of the mild and moderate stenosis groups were respectively examined by paired-sample t test. The differences in the changes of peak intensities and times to peak intensity on two sides between the mild and moderate stenosis groups were examined by independent samples t test. A p value less than 0.05 was considered statistically significant. 3. Results We measure the degrees of the stenosis in M1 segment of MCA on TOF MRA images. Figs. 1–3. A 47-year-old man. Mild stenosis in M1 segment of right MCA (arrow) was seen on TOF MRA (Fig. 1). The time intensity curves of left and right ROIs were seen on Figs. 2 and 3, respectively. The intensities and times to peak intensities of left and right ROIs were respectively 127.5, 927 ms and 122.3, 927 ms. Figs. 4–6. A 74-year-old woman. Moderate stenosis in M1 segment of right MCA (arrow) was seen on TOF MRA (Fig. 4). The time intensity curves of left and right ROIs were seen on Figs. 5 and 6, respectively. The peak intensities and times to peak intensities of left and right ROIs were respectively 88.2, 1209 ms and 84.6, 1459 ms. The peak intensities in ROIs on the normal and narrowed sides of mild stenosis group were 110.8 ± 9.39, 106.76 ± 11.92 (mean ± SD), respectively. The times to peak intensities of ROIs on normal and narrowed sides of mild stenosis group were 1037.28 ± 126.09 and 1071.76 ± 129.85, respectively. There were significant difference in the peak intensities (t = − 2.720, p = 0.011 b 0.05) and no significant difference in the times to peak intensities (t = − 1.279, p = 0.212 N 0.05) between normal and narrowed sides in mild stenosis group (Table 1). The peak intensities in ROIs on normal and narrowed sides of moderate stenosis group were 106.90 ± 11.46 and 98.77 ± 12.21, respectively. The times to peak intensities in ROIs on normal and narrowed sides of moderate stenosis group were 1021.09 ± 119.72 and 1237.09 ± 167.45, respectively. There were both significant
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difference in the peak intensities (t = −6.076, p = 0.000 b 0.05) and the times to peak intensities (t = 7.232, p = 0.000 b 0.05) between the normal and narrowed sides in moderate stenosis group (Table 2). The changes of peak intensities of mild and moderate stenosis groups were 3.30 ± 7.93 and 8.10 ± 6.54, respectively. The changes of times to peak intensities of mild and moderate stenosis groups were 34.48 ± 145.22 and 215.90 ± 159.90, respectively. There were both significant difference in the changes of peak intensities (t = − 2.11, p = 0.040 b 0.05) and times to peak intensities (t = − 4.23, p = 0.000 b 0.05) between mild and moderate stenosis group (Table 3).
4. Discussion
Fig. 1. A 47-year-old man with mild stenosis in M1 segment of right MCA. TOF MRA.
ASL techniques can be categorized into PASL, continuous ASL (CASL) and pseudo-continuous ASL (PCASL). The intrinsically low SNR of ASL has limited its application. Although CASL techniques have higher signal-to-noise ratio (SNR), they have been limited in
Fig. 2. A 47-year-old man with mild stenosis in M1 segment of right MCA. The PASL images and TIC curve of left ROIs.
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Fig. 3. A 47-year-old man with mild stenosis in M1 segment of right MCA. The PASL images and TIC curve of right ROIs.
Fig. 4. A 74-year-old woman with moderate stenosis in M1 segment of right MCA. TOF MRA.
clinical practice by high radiofrequency energy deposition and more demanding requirements from the scanner's hardware [15]. For most PASL techniques, the tagging efficiency is greater than 95% [16]. PCASL has been introduced as an intermediate means to take advantage of CASL's high SNR and PASL's high tagging efficiency. In recent years, the ease of implementation has made PASL a frequent use for neuroimaging [17,18]. The duration for the labeled tracer to travel from the labeling region to the imaging slices is known as arterial transit time (ATT). PASL is sensitive to ATT, which can either lead to over-estimation of CBF due to bright intravascular spins or under-estimation of CBF due to delayed arrival [19]. The display of dynamic signal changes can reduce these mistakes. High temporal resolution and SNR are needed to detect these signal changes in the arteries in this study. Great tagging efficiency can raise the signal intensities in the arteries and contribute to the improvement of SNR of the PASL images. Methods for improving temporal resolution include single-shot ASL [20], because the center of kspace is acquired during each acquisition. Multi-Td PASL imaging has the ability to improve temporal resolution using single-shot technique [10].
J. Chen et al. / Magnetic Resonance Imaging 32 (2014) 1277–1283
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Fig. 5. A 74-year-old woman with moderate stenosis in M1 segment of right MCA. The PASL images and TIC curve of left ROIs.
The ischemic symptoms in patients with cerebral artery stenosis can be caused by atheromatous thrombosis, embolic disease, vasculitis or vasospasm [21]. The hemodynamic changes in the arteries are correlated with the degrees of arterial stenosis. The results of our study showed that there were significant difference in the peak intensities and no significant difference in the times to peak intensities between normal and narrowed sides in mild stenosis group. Blood supply from MCA with mild stenosis were not delayed, but only decreased. There were both significant difference in the peak intensities and the times to peak intensities between normal and narrowed sides in moderate stenosis group. Blood supply from MCA with moderate stenosis were delayed and also decreased. The hemodynamic signal changes on multi-Td PASL images represent the changes of blood supply from narrowed arteries. We also found that there were both significant differences in the changes of peak intensities and times to peak intensities between mild and moderate stenosis groups. Moderate stenosis means greater hemodynamic changes in the arteries than mild stenosis. There was a limitation that patients with sever stenosis of MCA were not included in this study. The label interval and circle duration of multi-Td PASL sequence used in this study were 300 ms and
2000 ms, respectively. Blood flow was very slow when MCA were severely narrowed, so the peak signals in branches of MCA were out of acquisition. The prolongation of the delay times may be useful to detect the signal changes in cerebral arteries with sever stenosis. In conclusion, the hemodynamic changes were different with the degrees of cerebral artery stenosis. Moderate stenosis means greater dynamic changes in the arteries than mild stenosis. Multi-Td PASL imaging is a promising mean to demonstrate the hemodynamic changes of cerebral arteries with stenosis. The blood supply of brain from narrowed cerebral artery can be well displayed, which can provide useful information for clinical treatment.
References [1] Kasner SE, Chimowitz MI, Lynn MJ, et al. Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis. Circulation 2006;113: 555–63. [2] Duffis EJ, Jethwa P, Gupta G, et al. Accuracy of computed tomographic angiography compared to digital subtraction angiography in the diagnosis of intracranial stenosis and its impact on clinical decision-making. J Stroke Cerebrovasc Dis 2013;22:1013–7.
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Fig. 6. A 74-year-old woman with moderate stenosis in M1 segment of right MCA. The PASL images and TIC curve of right ROIs. Table 1 The peak intensities and times to peak intensities of mild stenosis group.
Peak intensities Times to peak intensities
Normal side
Narrowed side
t value
p value
110.8 ± 9.39 1037.28 ± 126.09
106.76 ± 11.92 1071.76 ± 129.85
−2.720 1.279
0.011 0.212
Table 2 The peak intensities and times to peak intensities of moderate stenosis group.
Peak intensities Times to peak intensities
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t value
p value
106.90 ± 11.46 1021.09 ± 119.72
98.77 ± 12.21 1237.09 ± 167.45
−6.076 7.232
0.000 0.000
Table 3 The changes of peak intensities and times to peak intensities. Mild stenosis group
Moderate stenosis group
t value p value
Peak intensities 3.30 ± 7.93 8.10 ± 6.54 −2.11 Times to peak intensities 34.48 ± 145.22 215.90 ± 159.90 −4.23
0.040 0.000
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