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Arterial spin-labeling in routine clinical practice: a preliminary experience of 200 cases and correlation with MRI and clinical findings
Clinical Imaging 36 (2012) 345 – 352
Arterial spin-labeling in routine clinical practice: a preliminary experience of 200 cases and correlation with MRI and clinical findings Tai-Yuan Chen a,⁎, Lee Chiu b , Tai-Ching Wu a , Te-Chang Wu a , Chien-Jen Lin a , Shih-Chuan Wu c , Yu-Kun Tsui a a
Section of Neuroradiology, Department of Medical Imaging, Chi-Mei Medical Center, Tainan, Taiwan b Providence Saint Joseph Medical Center; Hollywood Media Center, Burbank, California, USA c Department of Medical Imaging, Chi-Mei Medical Center, Tainan, Taiwan Received 13 July 2011; accepted 3 November 2011
Abstract We described our experience with a heterogeneous collection of 200 arterial spin-labeling (ASL) perfusion cases. ASL imaging was performed on a 1.5-T magnetic resonance imaging unit with a receive head coil using a second version of quantitative perfusion imaging. Sixty-four (32%) patients exhibited normal perfusion, 107 (53.5%) patients exhibited hypoperfusion, and 29 (14.5%) exhibited hyperperfusion. This ASL study illustrates the usefulness of ASL perfusion studies in a number of pathological conditions and that perfusion imaging can be implemented successfully in a routine clinical neuroimaging protocol. © 2012 Elsevier Inc. All rights reserved. Keywords: Arterial spin-labeling; MR perfusion technique; Hypoperfusion; Hyperperfusion
1. Introduction Dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI), computed tomography perfusion, positron emission tomography, and single photon emission computed tomography are all useful for the investigation of cerebral blood flow (CBF) in various disease states including cerebral infarctions, tumors, and seizure disorders [1]. Perfusion MRI, particularly DSC MRI, has been established as a valuable adjunct imaging technique for the evaluation of a wide variety of intracranial disease processes [1]. All of the aforementioned methods are associated with unique benefits and limitations [1]. Arterial spin-labeling (ASL) perfusion MRI, though in development for over a decade, has only recently become ⁎ Corresponding author. Section of Neuroradiology, Department of Medical Imaging, Chi-Mei Medical Center 901, Chung Hwa Road, Yong Kang City, Tainan County 710, Taiwan. Tel.: +886 6 2812811; fax: +886 6 2828142. E-mail address: [email protected] (T.-Y. Chen). 0899-7071/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.clinimag.2011.11.003
available as a clinical tool for the quantitative measurement of CBF [2,3]. ASL capitalizes on the freely diffusible property of arterial water, and the general principle of ASL is to measure the difference of arterial magnetization between a “tag” and “control” that is be proportional to the arterial blood delivered and consequently to the CBF [2,3]. ASL imaging can facilitate the identification of many neurological conditions such as stroke, Alzheimer's disease, brain tumors, carotid artery disorders, and dural arteriovenous malformations [4–10], and ASL has a number of benefits over other methods for determining CBF. ASL is noninvasive, repeatable, and performed without gadolinium, thus eliminating concerns of nephrogenic systemic fibrosis in patients with renal insufficiency [1,3,11]. Additionally, ASL allows for quantitative measurement of CBF and thus can be used for absolute identification of hypo- and hyperperfusion. Furthermore, repeat measurements can be performed with ASL, which may be required before and after cerebrovascular dilatation and other neurointerventional procedure. ASL methods also allow evaluation of functional brain activity [12], which is useful in the planning of neurosurgical
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procedures. Recent studies have found a good correlation between ASL and DSC MRI in the measurement of CBF [10]. Despite the advantages of ASL, disadvantages include a low signal-to-noise ratio compared with other perfusion imaging techniques and susceptibility to a number of artifact types [2]. The purpose of this retrospective study is to demonstrate alterations in brain perfusion as shown by ASL in a heterogeneous collection of neurological conditions and to illustrate the integration of ASL into a standard neuroimaging protocol.
2. Methods We retrospectively reviewed the medical records of 200 consecutive patients who received ASL perfusion scanning for the evaluation of intracranial pathology from September 2008 to December 2008. All patients received brain MRI, and ASL was included in the scanning protocol and performed in the same session before the standard MRI protocol. Patient demographic, clinical, and radiographic data were collected. This study was approved by the Institution Review Board of the Chi-Mei Medical Center, and the requirement of informed consent was waived due to the retrospective nature of the study. Patient informed consent was obtained for the MRI and ASL scanning procedures.
2.1. ASL method All ASL perfusion imaging examinations were performed on a clinical 1.5-T MRI unit (Avanto; Siemens, Germany) with a receive head coil using a second version of quantitative perfusion imaging by means of single subtraction with the addition of thin-section periodic saturation using Q2TIPS. Q2TIPS is a pulsed ASL method that enables the acquisition of multiple sections [13]. Q2TIPS has two important slabs (labeling and imaging) and three parameters [inversion time 1 (TI1), saturation stop time (TI1S), and inversion time 2 (TI2)]. The labeling slab is the region where the proximal arterial blood is labeled by an inversion radiofrequency pulse, i.e., 180° pulse. The imaging slab is the region where the acquisition of the perfusion imaging data is acquired. TI1 is a timing parameter representing the amount of time that passes between the inversion pulse for labeling the blood and the periodic saturation pulse; the periodic saturation pulse is applied to the distal 2 cm of the labeled slab. TI1S represents the amount of time between the inversion pulse for labeling and the end of the saturation pulse on the labeling slab. TI2 represents the amount of time between the inversion pulse for labeling and the beginning of the imaging data acquisition by an echo-planar imaging (EPI) sequence. The parameters used for imaging were as follows: echo time (TE), 16 ms; repetition time (TR), 2500 ms; receiver bandwidth, 1735 Hz; flip angle, 90°; field of view, 256 mm×256 mm; acquisition matrix, 64×64 (nine
Fig. 1. Normal ASL CBF mapping. Multisection JPEG map with color ramp representing units of ml/100 g tissue/min.
T.-Y. Chen et al. / Clinical Imaging 36 (2012) 345–352
sections, 8-mm thickness, 1-mm section gap); frequency encoding direction, right to left; TI1, 700 ms; TI1s, 1600 ms; TI2, 1800 ms; flow limit, 100 cm/s (added to suppress intraarterial spins); scan time, 230 s (in addition to MRI scan time). The number of tagged and control pairs averaged was 90 (45 for tagging, 45 for control). The perfusion images were generated by subtracting the labeled image from the nonlabeled image at each section position. Motion correction (3D PACE motion correction) was performed [2,14]. Postprocessing was fully automated, and output was a row subtraction image and relative CBF map. The standard MRI protocol included the following: T1WI, T2WI, fluidattenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI)/Apparent diffusion coefficient map, gradientecho image, and MR angiography and postcontrast T1WI if needed. The ASL studies were analyzed with respect to patterns of perfusion on final gray-scale DICOM images, and color Joint Photographic Experts Group (JPEG) CBF maps. A representative image of a normal study is shown in Fig. 1. The multisection JPEG map with color ramp represents units of ml/100 g tissue/min. In this study, we did not quantify perfusion, but compared the perfusion of the lesion with the contralateral side of the brain to estimate the perfusion pattern. On the JPEG CBF maps, if the color scale of the lesion was higher than the corresponding region on the contralateral side, it was defined as hyperperfusion; if the color scale of the lesion was lower, it was defined as hypoperfusion; and if there was no difference between the 2 sides, it was defined as normal perfusion. All images were reviewed by two experienced neuroradiologists who were blinded to the diagnosis and who arrived at a final evaluation and diagnosis by consensus. MRI and clinical data were compared to ASL findings.
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3. Results A total of 200 ASL studies were included in this study. There were 108 males (54%) and 92 females (46%) with a mean age of 55.6±17.7 years who received ASL perfusion examinations. Patient diagnoses included acute infarction (52 cases), brain atrophy (7 cases), encephalomalacia (21 cases), glioblastoma multiforme (GBM) (11 cases), headache with normal MRI (5 cases), hemifacial spasm with normal MRI (4 cases), hydrocephalus due to subarachnoid hemorrhage (SAH) (3 cases), intraparenchymal hemorrhage (5 cases), lymphoma (4 cases), meningioma (5 cases), metastasis (6 cases), pituitary adenoma (3 cases), SAH due to ruptured aneurysm (4 cases), seizure disorder with normal MRI (13 cases), suspected diffuse axonal injury with normal MRI (3 cases), suspected multiple sclerosis based on clinical symptoms with normal MRI (4 cases), transient ischemic attack (TIA)–intracranial artery stenosis (11 cases), transient memory loss with normal MRI (8 cases), vertigo with normal MRI (6 cases), and 15 other variable clinical entities totaling 25 additional cases. Sixty-four (32%) patients exhibited normal perfusion, 107 (53.5%) patients exhibited hypoperfusion, and 29 (14.5%) exhibited hyperperfusion on pulsed ASL perfusion scanning. ASL depicted either hypoperfusion or hyperperfusion in all 136 cases in which conventional MRI exhibited a pathological finding. Representative examples of hypoperfusion and clinical correlations are presented in Figs. 2 and 3. Causes of hypoperfusion identified on the ASL studies included acute cerebral ischemia (Fig. 2), chronic cerebral ischemia, TIA of the anterior and posterior circulation, hydrocephalus, and hematoma (Fig. 3). Representative examples of hyperperfusion and clinical correlations are presented in Figs. 4 through 6. Causes of hyperperfusion identified in the ASL studies
Fig. 2. Acute cerebral ischemia. Axial T2-weighted image (A) and diffusion-weighted image (B) show an acute infarct in the right cerebral hemisphere. MR angiography (C) demonstrates a right middle cerebral artery occlusion. ASL map (D) shows the right ischemic core (arrow) and ischemic penumbra (arrowhead). The area of diffusion restriction match on the ASL image and the DWI image is the infarct core.
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Fig. 3. Hematoma. Axial T2-weighted (A) and gradient-echo (B) images show intraparenchymal hemorrhage in the right cerebral hemisphere. Focal loss of signal intensity on the ASL map (C) (arrow) corresponds to the area of hemorrhage, resulting from a lack of vascularity and susceptibility effects associated with blood products.
Fig. 4. Glioblastoma multiforme. Axial postcontrast T1-weighted image (A) demonstrates a heterogeneous enhancing mass in the left cerebral hemisphere. Single-voxel MR spectroscopy (TE 144 ms) (B) reveals a malignant tumor spectrum. ASL map (C) shows corresponding hyperperfusion (arrow). A good correlation between ASL and DSC MR image (D) (arrowhead) in measuring tumor vascularity is noted. Malignant tumor spectrum: increased choline peak, 3.2 ppm; decreased N-acetyl aspartate (NAA) peak, 2.0 ppm; lactate peak, 1.33 ppm (inverted doublet).
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Fig. 5. Gliomatosis cerebri. Axial FLAIR image (A) demonstrates infiltrating mass lesions involving the left thalamus and left insular cortex and bilateral periventricular regions. Postcontrast T1-weighted image (B) reveals no obvious corresponding contrast enhancement. Single-voxel MR spectroscopy (TE 144 ms) (C) of the left thalamic lesion reveals a tumor spectrum. ASL map (D) shows corresponding hyperperfusion (arrow). Tumor spectrum: increased choline peak, 3.2 ppm; decreased NAA peak, 2.0 ppm.
Fig. 6. Developmental venous anomaly (DVA). Axial postcontrast T1-weighted (A) and susceptibility-weighted (B) images demonstrate a developmental venous anomaly in the left cerebral hemisphere. ASL map (C) shows corresponding gyral hyperperfusion (arrow). Hyperperfusion in the parenchyma adjacent to the DVA is a result of the high-flow state.
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Table 1 ASL perfusion patterns in the study patients Perfusion
Number of patients (%)
Normal perfusion Hypoperfusion
64 (32.0) 107 (53.5)
Hyperperfusion
29 (14.5)
Clinical conditions
Acute cerebral ischemia Chronic cerebral ischemia TIA (anterior and posterior circulation) Hydrocephalus Hematoma Glioblastoma multiforme Gliomatosis cerebri Developmental venous anomaly
included GBM (Fig. 4), gliomatosis cerebri (Fig. 5), and developmental venous anomaly (Fig. 6). A summary of perfusion findings and clinical conditions is presented in Table 1. Fig. 7 illustrates a case of recurrent oligodendroglioma. Though hyperperfusion would have been expected, neurosurgical hardware from prior surgery resulted in a hypoperfusion artifact.
4. Discussion In this study, we have illustrated the integration of ASL study into a routine MRI protocol and shown examples of ASL findings of hypo- and hyperperfusion in a number of pathological conditions, as well as artifacts that may result in certain circumstances. We believe that these findings clearly illustrate the clinical usefulness of ASL, as we found that ASL is capable of accurately depicting various states of both hypoperfusion and hyperperfusion in cases with known neuropathology. ASL is noninvasive, repeatable, and
performed without gadolinium, thus eliminating concerns of nephrogenic systemic fibrosis in patients with renal insufficiency. The 230-s scan time allows its use in the setting of hyperacute stroke, and repeat measurements can be performed with ASL. ASL utilizes endogenous water as a tracer, and in comparison to other methods for determining CBF, ASL requires no exogenous contrast agent and does not expose the patient to radiation [3]. The general principle of ASL is to measure the difference of arterial magnetization between “tag” and “control”; this difference is proportional to the arterial blood delivered and consequently to the CBF [3]. With ASL, protons in the blood in vessels outside of the imaging volume are labeled; a short waiting period, postlabeling delay, allows the blood to reach the parenchyma; and then the parenchyma is imaged in the labeled and unlabeled (control) state. The labeled and control images are subtracted, and the result is a measure of perfusion. The signal difference depends on a number of parameters that include the travel time of blood from the tagging region to the imaging plane, T1 of blood and tissue, and flow rate [3]. There are four types of ASL based on the technique that tags the inflowing blood: pulsed ASL, continuous ASL (CASL), pseudo-CASL, and velocity-selective ASL [3]. While the majority of perfusion techniques provide qualitative data, i.e., relative changes in CBF, cerebral blood volume (CBV), and meant transit time (MTT), ASL provides quantitative data, and these allow for the assessment of cerebral perfusion in regions as well as globally [2,3]. Quantification allows the identification of hypercapnia and hypoxia, and changes after treatments such as chemotherapy and thrombolysis or after treatments for seizures or migraines [2,3]. Studies have also suggested a correlation between perfusion values and characteristics of neoplasms [15].
Fig. 7. Recurrent oligodendroglioma. Axial T2-weighted (A) and postcontrast T1-weighted (B) images demonstrate a case of recurrent oligodendroglioma in the right cerebral hemisphere after previous tumor resection. ASL map (C) shows susceptibility artifact in the surgical bed (arrow) due to the neurosurgical hardware (arrowhead).
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Initial studies [10] of ASL performed in ischemic cerebrovascular disease such as infarctions and TIAs have demonstrated the feasibility of acquiring CBF maps using ASL in both acute and chronic conditions, with findings of hypoperfusion similar to those presented in Fig. 2. Much of the value of ASL is derived from its ability to image tissues at risk for ischemia or infarction, and regions that are potentially salvageable [4,8]. Although DWI is now the mainstay of stroke evaluation, it only provides information regarding the core area of severe ischemia. Detection of regions of mild or moderate ischemia, the ischemic penumbra, requires assessment of CBF. ASL CBF maps show this area as a larger region of diminished signal intensity, which may potentially gain the greatest benefit from thrombolytic strategies if identified in a timely fashion [4]. However, ASL-derived penumbra should be considered with caution as many questions are still unsolved on the correct definition of penumbra, even with DSC [2,4,8,16]. Moreover, low flows are more difficult to depict and quantify with ASL than higher flows [2,16]. Causes of a focal hypoperfusion pattern on ASL imaging include ischemic core and penumbra, at-risk tissue, leukoaraiosis, remote insult, seizure activity, and ventriculomegaly [4]. Causes of a global hypoperfusion pattern include poor cardiac output, vasospasm, brain death, cerebral atrophy, and exogenous drugs [4]. Identification of hypoperfusion has also been found to be useful in predicting and following the progression of cognitive decline [17]. The lack of normal vascularity in occlusive vascular disease and susceptibility effects associated with blood products can result in regional or global hypoperfusion [4,17]. Causes of hyperperfusion identified in the ASL studies included GBM (Fig. 4), gliomatosis cerebri (Fig. 5), and developmental venous anomaly (Fig. 6). ASL is sensitive in depicting focal hyperperfusion in a number of conditions including stroke, tumors, seizures, or loss of the autoregulatory function of blood vessels [5]. Recognized causes of a focal hyperperfusion pattern include luxury perfusion, reperfusion, spontaneous recanalization, thrombolyticinduced recanalization, seizure activity, vascular malformation, localized autoregulatory dysfunction, posterior reversible encephalopathy syndrome, migraine, postendarterectomy, inflammation, and infection [5]. Recognized causes of a global hyperperfusion pattern include young age, robust CBF, hypercapnia, postcarotid endarterectomy, and postanoxic insult [5]. Despite the clinical utility of ASL, there are some limitations of the technique that must be recognized. Most important is the relatively low signal-to-noise ratio of ASL, which is problematic with lack of patient cooperation and because of the number of artifacts associated with ASL. Hypoperfusion reduces the ASL signal magnitude, and the prolonged arterial transit time that typically accompanies hypoperfusion may also result in vascular artifact. Currently, we can use CASL to maximize perfusion contrast or use a longer postlabeling delay in patients with cerebrovascular
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disease/low-flow states to counteract the effect of delayed arterial transit time. The existing ASL technology can only provide the CBF data and is unable to provide data regarding CBV and MTT. Lastly, when first developed, clinical implementation of ASL was hampered by complex postprocessing requirements; however, these difficulties have been largely overcome, allowing ASL to become more widely available in clinical settings [3]. As with other EPI sequences, susceptibility artifact is a factor and is represented as a signal intensity void on ASL CBF maps. Metallic hardware, blood products (Fig. 3), and air may contribute to susceptibility effects [2,3]. Blood products produce a local gradient susceptibility artifact and may exaggerate the perfusion deficit in the hemorrhagic transformation of an infarct because of the paramagnetic effects. Conversely, hemorrhage in areas of reperfusion or vasomotor instability may mask the underlying high signal intensity on ASL CBF maps. In addition, the presence of neurosurgical hardware near a resection cavity (Fig. 7) represents a significant limitation of ASL in the evaluation of residual or recurrent disease because of magnetic field distortion [2]. Blooming and signal void from the intracranial calcifications may also hinder interpretation of blood flow on ASL maps, such as in the assessment of tumor vascularity in calcified meningiomas or oligodendrogliomas [2]. Low signal intensity in the inferior frontal lobes is commonly encountered because of the aerated paranasal sinuses and air–bone interfaces at the skull base [2]. This effect is less pronounced in the pediatric age group because of nonaerated sinuses, which may in part explain the higher global CBF values commonly seen in this population [5]. However, in children, an increased signalto-noise ratio as compared to that found in adults is typically seen [2]. Regional increases in signal intensity in the occipital lobes have also been described and are suggested to be a result of stimulation during the MRI procedure [2]. Motion artifact is also a concern with ASL scanning; even slight movements can impact the quality of imaging data [2,3]. The system used at our institution uses a proprietary software to minimize motion artifacts [14]. Other artifacts that can occur with ASL include spin-label decay, which can result in lower perfusion signal intensity in the more rostral images because sections acquired at the end of the volume contain less label than those acquired at the beginning; the tissue-masking effect, which can result in relevant portions of the image being lost in cases with high signal intensity due to gadolinium enhancement (e.g., tumors); the gadolinium artifact, which due to shortening of T1 in all tissues decreases the measurable difference between the spin tag and control; and the coil sensitivity artifact, which is typically the result of patient head positioning or asymmetric coil sensitivity in the array and can result in regional differences in signal intensity [2]. Familiarity with commonly encountered artifacts and normal variants can help avoid pitfalls in the interpretation of CBF maps.
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A limitation of this report that should be considered is that this is a descriptive analysis obtained through a retrospective review of medical records and imaging data. No statistical analysis was performed. However, correlation of ASL findings with MRI and clinical data clearly illustrates the findings of ASL studies in a number of common clinical conditions. 5. Conclusions In summary, this review of ASL studies illustrates the usefulness of ASL perfusion studies in a number of pathological conditions and that perfusion imaging can be implemented successfully in a routine clinical neuroimaging protocol. Knowledge of artifacts and their causes is important for correct interpretation of imaging findings. While ASL cannot currently replace DSC PWI technology, it provides another option for determining perfusion that may be especially useful in certain cases such as patients with poor renal function and stroke and for evaluating treatments. Further study of the utility of ASL in clinical practice is certainly warranted. References [1] Wintermark M, Sesay M, Barbier E, Borbély K, Dillon WP, Eastwood JD, Glenn TC, Grandin CB, Pedraza S, Soustiel JF, Nariai T, Zaharchuk G, Caillé JM, Dousset V, Yonas H. Comparative overview of brain perfusion imaging techniques. J Neuroradiol 2005;32: 294–314. [2] Deibler AR, Pollock JM, Kraft RA, Tan H, Burdette JH, Maldjian JA. Arterial spin-labeling in routine clinical practice, part 1: technique and artifacts. AJNR Am J Neuroradiol 2008;29:1228–34. [3] Pollock JM, Tan H, Kraft RA, Whitlow CT, Burdette JH, Maldjian JA. Arterial spin-labeled MR perfusion imaging: clinical applications. Magn Reson Imaging Clin N Am 2009;17(2):315–38. [4] Deibler AR, Pollock JM, Kraft RA, Tan H, Burdette JH, Maldjian JA. Arterial spin-labeling in routine clinical practice, part 2: hypoperfusion patterns. AJNR Am J Neuroradiol 2008;29:1235–41. [5] Deibler AR, Pollock JM, Kraft RA, Tan H, Burdette JH, Maldjian JA. Arterial spin-labeling in routine clinical practice, part 3: hyperperfusion patterns. AJNR Am J Neuroradiol 2008;29:1428–35.
[6] Johnson NA, Jahng GH, Weiner MW, Miller BL, Chui HC, Jagust WJ, Gorno-Tempini ML, Schuff N. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience. Radiology 2005; 234(3):851–9. [7] Warmuth C, Gunther M, Zimmer C. Quantification of blood flow in brain tumors: comparison of arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging. Radiology 2003;228:523–32. [8] Zaharchuk G, Bammer R, Straka M, Shankaranarayan A, Alsop DC, Fischbein NJ, Atlas SW, Moseley ME. Arterial spin-label imaging in patients with normal bolus perfusion-weighted MR imaging findings: pilot identification of the borderzone sign. Radiology 2009;252(3): 797–807. [9] Tourdias T, Rodrigo S, Oppenheim C, Naggara O, Varlet P, Amoussa S, Calmon G, Roux FX, Meder JF. Pulsed arterial spin labeling applications in brain tumors: practical review. J Neuroradiol 2008; 35(2):79–89. [10] Wolf RL, Alsop DC, McGarvey ML, Maldjian JA, Wang J, Detre JA. Susceptibility contrast and arterial spin labeled perfusion MRI in cerebrovascular disease. J Neuroimaging 2003;13:17–27. [11] Sadowski EA, Bennett LK, Chan MR, Wentland AL, Garrett AL, Garrett RW, Djamali A. Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology 2007;243:148–57. [12] Silva AC, Kim SG. Perfusion-based functional magnetic resonance imaging. Concepts Magn Reson Part A 2003;16A:16–27. [13] Luh WM, Wong EC, Bandettini PA, Hyde JS. QUIPSS II with thinslice TI1 periodic saturation: a method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling. Magn Reson Med 1999;41:1246–54. [14] 3D PACE (Prospective Acquisition CorrEction). Siemens USA. Available at: https://www.medical.siemens.com/webapp/wcs/stores/ servlet/PSOptionProductDisplayView?catalogId=-1&catTree= 100010,1007660,12754,1024365&langId=-1&productId=191084& productType=6&storeId=10001. Accessed September 2010. [15] Noguchi T, Yoshiura T, Hiwatashi A, Togao O, Yamashita K, Nagao E, Shono T, Mizoguchi M, Nagata S, Sasaki T, Suzuki SO, Iwaki T, Kobayashi K, Mihara F, Honda H. Perfusion imaging of brain tumors using arterial spin labeling: correlation with histopathologic vascular density. AJNR Am J Neuroradiol 2008;29:688–93. [16] Parkes LM, Rashid W, Chard DT, Tofts PS. Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects. Magn Reson Med 2004;51: 736–43. [17] Chao LL, Buckley ST, Kornak J, Schuff N, Madison C, Yaffe K, Miller BL, Kramer JH, Weiner MW. ASL perfusion MRI predicts cognitive decline and conversion from MCI to dementia. Alzheimer Dis Assoc Disord 2010;24(1):19–27.
Arterial spin-labeling in routine clinical practice: a preliminary experience of 200 cases and correlation with MRI and clinical findings Tai-Yuan Chen a,⁎, Lee Chiu b , Tai-Ching Wu a , Te-Chang Wu a , Chien-Jen Lin a , Shih-Chuan Wu c , Yu-Kun Tsui a a
Section of Neuroradiology, Department of Medical Imaging, Chi-Mei Medical Center, Tainan, Taiwan b Providence Saint Joseph Medical Center; Hollywood Media Center, Burbank, California, USA c Department of Medical Imaging, Chi-Mei Medical Center, Tainan, Taiwan Received 13 July 2011; accepted 3 November 2011
Abstract We described our experience with a heterogeneous collection of 200 arterial spin-labeling (ASL) perfusion cases. ASL imaging was performed on a 1.5-T magnetic resonance imaging unit with a receive head coil using a second version of quantitative perfusion imaging. Sixty-four (32%) patients exhibited normal perfusion, 107 (53.5%) patients exhibited hypoperfusion, and 29 (14.5%) exhibited hyperperfusion. This ASL study illustrates the usefulness of ASL perfusion studies in a number of pathological conditions and that perfusion imaging can be implemented successfully in a routine clinical neuroimaging protocol. © 2012 Elsevier Inc. All rights reserved. Keywords: Arterial spin-labeling; MR perfusion technique; Hypoperfusion; Hyperperfusion
1. Introduction Dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI), computed tomography perfusion, positron emission tomography, and single photon emission computed tomography are all useful for the investigation of cerebral blood flow (CBF) in various disease states including cerebral infarctions, tumors, and seizure disorders [1]. Perfusion MRI, particularly DSC MRI, has been established as a valuable adjunct imaging technique for the evaluation of a wide variety of intracranial disease processes [1]. All of the aforementioned methods are associated with unique benefits and limitations [1]. Arterial spin-labeling (ASL) perfusion MRI, though in development for over a decade, has only recently become ⁎ Corresponding author. Section of Neuroradiology, Department of Medical Imaging, Chi-Mei Medical Center 901, Chung Hwa Road, Yong Kang City, Tainan County 710, Taiwan. Tel.: +886 6 2812811; fax: +886 6 2828142. E-mail address: [email protected] (T.-Y. Chen). 0899-7071/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.clinimag.2011.11.003
available as a clinical tool for the quantitative measurement of CBF [2,3]. ASL capitalizes on the freely diffusible property of arterial water, and the general principle of ASL is to measure the difference of arterial magnetization between a “tag” and “control” that is be proportional to the arterial blood delivered and consequently to the CBF [2,3]. ASL imaging can facilitate the identification of many neurological conditions such as stroke, Alzheimer's disease, brain tumors, carotid artery disorders, and dural arteriovenous malformations [4–10], and ASL has a number of benefits over other methods for determining CBF. ASL is noninvasive, repeatable, and performed without gadolinium, thus eliminating concerns of nephrogenic systemic fibrosis in patients with renal insufficiency [1,3,11]. Additionally, ASL allows for quantitative measurement of CBF and thus can be used for absolute identification of hypo- and hyperperfusion. Furthermore, repeat measurements can be performed with ASL, which may be required before and after cerebrovascular dilatation and other neurointerventional procedure. ASL methods also allow evaluation of functional brain activity [12], which is useful in the planning of neurosurgical
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procedures. Recent studies have found a good correlation between ASL and DSC MRI in the measurement of CBF [10]. Despite the advantages of ASL, disadvantages include a low signal-to-noise ratio compared with other perfusion imaging techniques and susceptibility to a number of artifact types [2]. The purpose of this retrospective study is to demonstrate alterations in brain perfusion as shown by ASL in a heterogeneous collection of neurological conditions and to illustrate the integration of ASL into a standard neuroimaging protocol.
2. Methods We retrospectively reviewed the medical records of 200 consecutive patients who received ASL perfusion scanning for the evaluation of intracranial pathology from September 2008 to December 2008. All patients received brain MRI, and ASL was included in the scanning protocol and performed in the same session before the standard MRI protocol. Patient demographic, clinical, and radiographic data were collected. This study was approved by the Institution Review Board of the Chi-Mei Medical Center, and the requirement of informed consent was waived due to the retrospective nature of the study. Patient informed consent was obtained for the MRI and ASL scanning procedures.
2.1. ASL method All ASL perfusion imaging examinations were performed on a clinical 1.5-T MRI unit (Avanto; Siemens, Germany) with a receive head coil using a second version of quantitative perfusion imaging by means of single subtraction with the addition of thin-section periodic saturation using Q2TIPS. Q2TIPS is a pulsed ASL method that enables the acquisition of multiple sections [13]. Q2TIPS has two important slabs (labeling and imaging) and three parameters [inversion time 1 (TI1), saturation stop time (TI1S), and inversion time 2 (TI2)]. The labeling slab is the region where the proximal arterial blood is labeled by an inversion radiofrequency pulse, i.e., 180° pulse. The imaging slab is the region where the acquisition of the perfusion imaging data is acquired. TI1 is a timing parameter representing the amount of time that passes between the inversion pulse for labeling the blood and the periodic saturation pulse; the periodic saturation pulse is applied to the distal 2 cm of the labeled slab. TI1S represents the amount of time between the inversion pulse for labeling and the end of the saturation pulse on the labeling slab. TI2 represents the amount of time between the inversion pulse for labeling and the beginning of the imaging data acquisition by an echo-planar imaging (EPI) sequence. The parameters used for imaging were as follows: echo time (TE), 16 ms; repetition time (TR), 2500 ms; receiver bandwidth, 1735 Hz; flip angle, 90°; field of view, 256 mm×256 mm; acquisition matrix, 64×64 (nine
Fig. 1. Normal ASL CBF mapping. Multisection JPEG map with color ramp representing units of ml/100 g tissue/min.
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sections, 8-mm thickness, 1-mm section gap); frequency encoding direction, right to left; TI1, 700 ms; TI1s, 1600 ms; TI2, 1800 ms; flow limit, 100 cm/s (added to suppress intraarterial spins); scan time, 230 s (in addition to MRI scan time). The number of tagged and control pairs averaged was 90 (45 for tagging, 45 for control). The perfusion images were generated by subtracting the labeled image from the nonlabeled image at each section position. Motion correction (3D PACE motion correction) was performed [2,14]. Postprocessing was fully automated, and output was a row subtraction image and relative CBF map. The standard MRI protocol included the following: T1WI, T2WI, fluidattenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI)/Apparent diffusion coefficient map, gradientecho image, and MR angiography and postcontrast T1WI if needed. The ASL studies were analyzed with respect to patterns of perfusion on final gray-scale DICOM images, and color Joint Photographic Experts Group (JPEG) CBF maps. A representative image of a normal study is shown in Fig. 1. The multisection JPEG map with color ramp represents units of ml/100 g tissue/min. In this study, we did not quantify perfusion, but compared the perfusion of the lesion with the contralateral side of the brain to estimate the perfusion pattern. On the JPEG CBF maps, if the color scale of the lesion was higher than the corresponding region on the contralateral side, it was defined as hyperperfusion; if the color scale of the lesion was lower, it was defined as hypoperfusion; and if there was no difference between the 2 sides, it was defined as normal perfusion. All images were reviewed by two experienced neuroradiologists who were blinded to the diagnosis and who arrived at a final evaluation and diagnosis by consensus. MRI and clinical data were compared to ASL findings.
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3. Results A total of 200 ASL studies were included in this study. There were 108 males (54%) and 92 females (46%) with a mean age of 55.6±17.7 years who received ASL perfusion examinations. Patient diagnoses included acute infarction (52 cases), brain atrophy (7 cases), encephalomalacia (21 cases), glioblastoma multiforme (GBM) (11 cases), headache with normal MRI (5 cases), hemifacial spasm with normal MRI (4 cases), hydrocephalus due to subarachnoid hemorrhage (SAH) (3 cases), intraparenchymal hemorrhage (5 cases), lymphoma (4 cases), meningioma (5 cases), metastasis (6 cases), pituitary adenoma (3 cases), SAH due to ruptured aneurysm (4 cases), seizure disorder with normal MRI (13 cases), suspected diffuse axonal injury with normal MRI (3 cases), suspected multiple sclerosis based on clinical symptoms with normal MRI (4 cases), transient ischemic attack (TIA)–intracranial artery stenosis (11 cases), transient memory loss with normal MRI (8 cases), vertigo with normal MRI (6 cases), and 15 other variable clinical entities totaling 25 additional cases. Sixty-four (32%) patients exhibited normal perfusion, 107 (53.5%) patients exhibited hypoperfusion, and 29 (14.5%) exhibited hyperperfusion on pulsed ASL perfusion scanning. ASL depicted either hypoperfusion or hyperperfusion in all 136 cases in which conventional MRI exhibited a pathological finding. Representative examples of hypoperfusion and clinical correlations are presented in Figs. 2 and 3. Causes of hypoperfusion identified on the ASL studies included acute cerebral ischemia (Fig. 2), chronic cerebral ischemia, TIA of the anterior and posterior circulation, hydrocephalus, and hematoma (Fig. 3). Representative examples of hyperperfusion and clinical correlations are presented in Figs. 4 through 6. Causes of hyperperfusion identified in the ASL studies
Fig. 2. Acute cerebral ischemia. Axial T2-weighted image (A) and diffusion-weighted image (B) show an acute infarct in the right cerebral hemisphere. MR angiography (C) demonstrates a right middle cerebral artery occlusion. ASL map (D) shows the right ischemic core (arrow) and ischemic penumbra (arrowhead). The area of diffusion restriction match on the ASL image and the DWI image is the infarct core.
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Fig. 3. Hematoma. Axial T2-weighted (A) and gradient-echo (B) images show intraparenchymal hemorrhage in the right cerebral hemisphere. Focal loss of signal intensity on the ASL map (C) (arrow) corresponds to the area of hemorrhage, resulting from a lack of vascularity and susceptibility effects associated with blood products.
Fig. 4. Glioblastoma multiforme. Axial postcontrast T1-weighted image (A) demonstrates a heterogeneous enhancing mass in the left cerebral hemisphere. Single-voxel MR spectroscopy (TE 144 ms) (B) reveals a malignant tumor spectrum. ASL map (C) shows corresponding hyperperfusion (arrow). A good correlation between ASL and DSC MR image (D) (arrowhead) in measuring tumor vascularity is noted. Malignant tumor spectrum: increased choline peak, 3.2 ppm; decreased N-acetyl aspartate (NAA) peak, 2.0 ppm; lactate peak, 1.33 ppm (inverted doublet).
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Fig. 5. Gliomatosis cerebri. Axial FLAIR image (A) demonstrates infiltrating mass lesions involving the left thalamus and left insular cortex and bilateral periventricular regions. Postcontrast T1-weighted image (B) reveals no obvious corresponding contrast enhancement. Single-voxel MR spectroscopy (TE 144 ms) (C) of the left thalamic lesion reveals a tumor spectrum. ASL map (D) shows corresponding hyperperfusion (arrow). Tumor spectrum: increased choline peak, 3.2 ppm; decreased NAA peak, 2.0 ppm.
Fig. 6. Developmental venous anomaly (DVA). Axial postcontrast T1-weighted (A) and susceptibility-weighted (B) images demonstrate a developmental venous anomaly in the left cerebral hemisphere. ASL map (C) shows corresponding gyral hyperperfusion (arrow). Hyperperfusion in the parenchyma adjacent to the DVA is a result of the high-flow state.
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Table 1 ASL perfusion patterns in the study patients Perfusion
Number of patients (%)
Normal perfusion Hypoperfusion
64 (32.0) 107 (53.5)
Hyperperfusion
29 (14.5)
Clinical conditions
Acute cerebral ischemia Chronic cerebral ischemia TIA (anterior and posterior circulation) Hydrocephalus Hematoma Glioblastoma multiforme Gliomatosis cerebri Developmental venous anomaly
included GBM (Fig. 4), gliomatosis cerebri (Fig. 5), and developmental venous anomaly (Fig. 6). A summary of perfusion findings and clinical conditions is presented in Table 1. Fig. 7 illustrates a case of recurrent oligodendroglioma. Though hyperperfusion would have been expected, neurosurgical hardware from prior surgery resulted in a hypoperfusion artifact.
4. Discussion In this study, we have illustrated the integration of ASL study into a routine MRI protocol and shown examples of ASL findings of hypo- and hyperperfusion in a number of pathological conditions, as well as artifacts that may result in certain circumstances. We believe that these findings clearly illustrate the clinical usefulness of ASL, as we found that ASL is capable of accurately depicting various states of both hypoperfusion and hyperperfusion in cases with known neuropathology. ASL is noninvasive, repeatable, and
performed without gadolinium, thus eliminating concerns of nephrogenic systemic fibrosis in patients with renal insufficiency. The 230-s scan time allows its use in the setting of hyperacute stroke, and repeat measurements can be performed with ASL. ASL utilizes endogenous water as a tracer, and in comparison to other methods for determining CBF, ASL requires no exogenous contrast agent and does not expose the patient to radiation [3]. The general principle of ASL is to measure the difference of arterial magnetization between “tag” and “control”; this difference is proportional to the arterial blood delivered and consequently to the CBF [3]. With ASL, protons in the blood in vessels outside of the imaging volume are labeled; a short waiting period, postlabeling delay, allows the blood to reach the parenchyma; and then the parenchyma is imaged in the labeled and unlabeled (control) state. The labeled and control images are subtracted, and the result is a measure of perfusion. The signal difference depends on a number of parameters that include the travel time of blood from the tagging region to the imaging plane, T1 of blood and tissue, and flow rate [3]. There are four types of ASL based on the technique that tags the inflowing blood: pulsed ASL, continuous ASL (CASL), pseudo-CASL, and velocity-selective ASL [3]. While the majority of perfusion techniques provide qualitative data, i.e., relative changes in CBF, cerebral blood volume (CBV), and meant transit time (MTT), ASL provides quantitative data, and these allow for the assessment of cerebral perfusion in regions as well as globally [2,3]. Quantification allows the identification of hypercapnia and hypoxia, and changes after treatments such as chemotherapy and thrombolysis or after treatments for seizures or migraines [2,3]. Studies have also suggested a correlation between perfusion values and characteristics of neoplasms [15].
Fig. 7. Recurrent oligodendroglioma. Axial T2-weighted (A) and postcontrast T1-weighted (B) images demonstrate a case of recurrent oligodendroglioma in the right cerebral hemisphere after previous tumor resection. ASL map (C) shows susceptibility artifact in the surgical bed (arrow) due to the neurosurgical hardware (arrowhead).
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Initial studies [10] of ASL performed in ischemic cerebrovascular disease such as infarctions and TIAs have demonstrated the feasibility of acquiring CBF maps using ASL in both acute and chronic conditions, with findings of hypoperfusion similar to those presented in Fig. 2. Much of the value of ASL is derived from its ability to image tissues at risk for ischemia or infarction, and regions that are potentially salvageable [4,8]. Although DWI is now the mainstay of stroke evaluation, it only provides information regarding the core area of severe ischemia. Detection of regions of mild or moderate ischemia, the ischemic penumbra, requires assessment of CBF. ASL CBF maps show this area as a larger region of diminished signal intensity, which may potentially gain the greatest benefit from thrombolytic strategies if identified in a timely fashion [4]. However, ASL-derived penumbra should be considered with caution as many questions are still unsolved on the correct definition of penumbra, even with DSC [2,4,8,16]. Moreover, low flows are more difficult to depict and quantify with ASL than higher flows [2,16]. Causes of a focal hypoperfusion pattern on ASL imaging include ischemic core and penumbra, at-risk tissue, leukoaraiosis, remote insult, seizure activity, and ventriculomegaly [4]. Causes of a global hypoperfusion pattern include poor cardiac output, vasospasm, brain death, cerebral atrophy, and exogenous drugs [4]. Identification of hypoperfusion has also been found to be useful in predicting and following the progression of cognitive decline [17]. The lack of normal vascularity in occlusive vascular disease and susceptibility effects associated with blood products can result in regional or global hypoperfusion [4,17]. Causes of hyperperfusion identified in the ASL studies included GBM (Fig. 4), gliomatosis cerebri (Fig. 5), and developmental venous anomaly (Fig. 6). ASL is sensitive in depicting focal hyperperfusion in a number of conditions including stroke, tumors, seizures, or loss of the autoregulatory function of blood vessels [5]. Recognized causes of a focal hyperperfusion pattern include luxury perfusion, reperfusion, spontaneous recanalization, thrombolyticinduced recanalization, seizure activity, vascular malformation, localized autoregulatory dysfunction, posterior reversible encephalopathy syndrome, migraine, postendarterectomy, inflammation, and infection [5]. Recognized causes of a global hyperperfusion pattern include young age, robust CBF, hypercapnia, postcarotid endarterectomy, and postanoxic insult [5]. Despite the clinical utility of ASL, there are some limitations of the technique that must be recognized. Most important is the relatively low signal-to-noise ratio of ASL, which is problematic with lack of patient cooperation and because of the number of artifacts associated with ASL. Hypoperfusion reduces the ASL signal magnitude, and the prolonged arterial transit time that typically accompanies hypoperfusion may also result in vascular artifact. Currently, we can use CASL to maximize perfusion contrast or use a longer postlabeling delay in patients with cerebrovascular
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disease/low-flow states to counteract the effect of delayed arterial transit time. The existing ASL technology can only provide the CBF data and is unable to provide data regarding CBV and MTT. Lastly, when first developed, clinical implementation of ASL was hampered by complex postprocessing requirements; however, these difficulties have been largely overcome, allowing ASL to become more widely available in clinical settings [3]. As with other EPI sequences, susceptibility artifact is a factor and is represented as a signal intensity void on ASL CBF maps. Metallic hardware, blood products (Fig. 3), and air may contribute to susceptibility effects [2,3]. Blood products produce a local gradient susceptibility artifact and may exaggerate the perfusion deficit in the hemorrhagic transformation of an infarct because of the paramagnetic effects. Conversely, hemorrhage in areas of reperfusion or vasomotor instability may mask the underlying high signal intensity on ASL CBF maps. In addition, the presence of neurosurgical hardware near a resection cavity (Fig. 7) represents a significant limitation of ASL in the evaluation of residual or recurrent disease because of magnetic field distortion [2]. Blooming and signal void from the intracranial calcifications may also hinder interpretation of blood flow on ASL maps, such as in the assessment of tumor vascularity in calcified meningiomas or oligodendrogliomas [2]. Low signal intensity in the inferior frontal lobes is commonly encountered because of the aerated paranasal sinuses and air–bone interfaces at the skull base [2]. This effect is less pronounced in the pediatric age group because of nonaerated sinuses, which may in part explain the higher global CBF values commonly seen in this population [5]. However, in children, an increased signalto-noise ratio as compared to that found in adults is typically seen [2]. Regional increases in signal intensity in the occipital lobes have also been described and are suggested to be a result of stimulation during the MRI procedure [2]. Motion artifact is also a concern with ASL scanning; even slight movements can impact the quality of imaging data [2,3]. The system used at our institution uses a proprietary software to minimize motion artifacts [14]. Other artifacts that can occur with ASL include spin-label decay, which can result in lower perfusion signal intensity in the more rostral images because sections acquired at the end of the volume contain less label than those acquired at the beginning; the tissue-masking effect, which can result in relevant portions of the image being lost in cases with high signal intensity due to gadolinium enhancement (e.g., tumors); the gadolinium artifact, which due to shortening of T1 in all tissues decreases the measurable difference between the spin tag and control; and the coil sensitivity artifact, which is typically the result of patient head positioning or asymmetric coil sensitivity in the array and can result in regional differences in signal intensity [2]. Familiarity with commonly encountered artifacts and normal variants can help avoid pitfalls in the interpretation of CBF maps.
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A limitation of this report that should be considered is that this is a descriptive analysis obtained through a retrospective review of medical records and imaging data. No statistical analysis was performed. However, correlation of ASL findings with MRI and clinical data clearly illustrates the findings of ASL studies in a number of common clinical conditions. 5. Conclusions In summary, this review of ASL studies illustrates the usefulness of ASL perfusion studies in a number of pathological conditions and that perfusion imaging can be implemented successfully in a routine clinical neuroimaging protocol. Knowledge of artifacts and their causes is important for correct interpretation of imaging findings. While ASL cannot currently replace DSC PWI technology, it provides another option for determining perfusion that may be especially useful in certain cases such as patients with poor renal function and stroke and for evaluating treatments. Further study of the utility of ASL in clinical practice is certainly warranted. References [1] Wintermark M, Sesay M, Barbier E, Borbély K, Dillon WP, Eastwood JD, Glenn TC, Grandin CB, Pedraza S, Soustiel JF, Nariai T, Zaharchuk G, Caillé JM, Dousset V, Yonas H. Comparative overview of brain perfusion imaging techniques. J Neuroradiol 2005;32: 294–314. [2] Deibler AR, Pollock JM, Kraft RA, Tan H, Burdette JH, Maldjian JA. Arterial spin-labeling in routine clinical practice, part 1: technique and artifacts. AJNR Am J Neuroradiol 2008;29:1228–34. [3] Pollock JM, Tan H, Kraft RA, Whitlow CT, Burdette JH, Maldjian JA. Arterial spin-labeled MR perfusion imaging: clinical applications. Magn Reson Imaging Clin N Am 2009;17(2):315–38. [4] Deibler AR, Pollock JM, Kraft RA, Tan H, Burdette JH, Maldjian JA. Arterial spin-labeling in routine clinical practice, part 2: hypoperfusion patterns. AJNR Am J Neuroradiol 2008;29:1235–41. [5] Deibler AR, Pollock JM, Kraft RA, Tan H, Burdette JH, Maldjian JA. Arterial spin-labeling in routine clinical practice, part 3: hyperperfusion patterns. AJNR Am J Neuroradiol 2008;29:1428–35.
[6] Johnson NA, Jahng GH, Weiner MW, Miller BL, Chui HC, Jagust WJ, Gorno-Tempini ML, Schuff N. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience. Radiology 2005; 234(3):851–9. [7] Warmuth C, Gunther M, Zimmer C. Quantification of blood flow in brain tumors: comparison of arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging. Radiology 2003;228:523–32. [8] Zaharchuk G, Bammer R, Straka M, Shankaranarayan A, Alsop DC, Fischbein NJ, Atlas SW, Moseley ME. Arterial spin-label imaging in patients with normal bolus perfusion-weighted MR imaging findings: pilot identification of the borderzone sign. Radiology 2009;252(3): 797–807. [9] Tourdias T, Rodrigo S, Oppenheim C, Naggara O, Varlet P, Amoussa S, Calmon G, Roux FX, Meder JF. Pulsed arterial spin labeling applications in brain tumors: practical review. J Neuroradiol 2008; 35(2):79–89. [10] Wolf RL, Alsop DC, McGarvey ML, Maldjian JA, Wang J, Detre JA. Susceptibility contrast and arterial spin labeled perfusion MRI in cerebrovascular disease. J Neuroimaging 2003;13:17–27. [11] Sadowski EA, Bennett LK, Chan MR, Wentland AL, Garrett AL, Garrett RW, Djamali A. Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology 2007;243:148–57. [12] Silva AC, Kim SG. Perfusion-based functional magnetic resonance imaging. Concepts Magn Reson Part A 2003;16A:16–27. [13] Luh WM, Wong EC, Bandettini PA, Hyde JS. QUIPSS II with thinslice TI1 periodic saturation: a method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling. Magn Reson Med 1999;41:1246–54. [14] 3D PACE (Prospective Acquisition CorrEction). Siemens USA. Available at: https://www.medical.siemens.com/webapp/wcs/stores/ servlet/PSOptionProductDisplayView?catalogId=-1&catTree= 100010,1007660,12754,1024365&langId=-1&productId=191084& productType=6&storeId=10001. Accessed September 2010. [15] Noguchi T, Yoshiura T, Hiwatashi A, Togao O, Yamashita K, Nagao E, Shono T, Mizoguchi M, Nagata S, Sasaki T, Suzuki SO, Iwaki T, Kobayashi K, Mihara F, Honda H. Perfusion imaging of brain tumors using arterial spin labeling: correlation with histopathologic vascular density. AJNR Am J Neuroradiol 2008;29:688–93. [16] Parkes LM, Rashid W, Chard DT, Tofts PS. Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects. Magn Reson Med 2004;51: 736–43. [17] Chao LL, Buckley ST, Kornak J, Schuff N, Madison C, Yaffe K, Miller BL, Kramer JH, Weiner MW. ASL perfusion MRI predicts cognitive decline and conversion from MCI to dementia. Alzheimer Dis Assoc Disord 2010;24(1):19–27.