Korean J Radiol.  2014 Oct;15(5):554-577. 10.3348/kjr.2014.15.5.554.

Perfusion Magnetic Resonance Imaging: A Comprehensive Update on Principles and Techniques

• Jahng GH
• Li KL
• Ostergaard L
• Calamante

• KMID: 1734941
• DOI: http://doi.org/10.3348/kjr.2014.15.5.554

Abstract

Perfusion is a fundamental biological function that refers to the delivery of oxygen and nutrients to tissue by means of blood flow. Perfusion MRI is sensitive to microvasculature and has been applied in a wide variety of clinical applications, including the classification of tumors, identification of stroke regions, and characterization of other diseases. Perfusion MRI techniques are classified with or without using an exogenous contrast agent. Bolus methods, with injections of a contrast agent, provide better sensitivity with higher spatial resolution, and are therefore more widely used in clinical applications. However, arterial spin-labeling methods provide a unique opportunity to measure cerebral blood flow without requiring an exogenous contrast agent and have better accuracy for quantification. Importantly, MRI-based perfusion measurements are minimally invasive overall, and do not use any radiation and radioisotopes. In this review, we describe the principles and techniques of perfusion MRI. This review summarizes comprehensive updated knowledge on the physical principles and techniques of perfusion MRI.

Keyword

Perfusion; Perfusion MRI; Dynamic susceptibility contrast; Dynamic contrast-enhanced; Arterial spin-labeling

MeSH Terms

Arteries/chemistry
Brain Neoplasms/radiography
Contrast Media/diagnostic use
Humans
Magnetic Resonance Imaging/standards/*trends
Spin Labels
Stroke/radiography
Contrast Media
Spin Labels

Figure

• 

  Fig. 1 Hemodynamics of contrast agent obtained with dynamic susceptibility contrast MRI signal intensity time course (in arbitrary units), for voxel. Series images are acquired before, during, and after injecting contrast agent. While passing through microvasculature, bolus of contrast agent produces decreases in magnetic resonance signal intensity.

• 

  Fig. 2 Hemodynamics of contrast agent obtained with dynamic contrast-enhanced MRI signal intensity time course (in arbitrary units), for voxel. Time course of enhancement is depended on physiological parameters of microvasculature in lesion, and on volume fractions of various tissue compartments. For bolus injection of contrast agent into blood circulation, there is always initial increase in its concentration in plasma.

• 

  Fig. 3 Subtracted hemodynamic signal between control and labeled images on arterial spin labeling (ASL) experiment. Curve shows three phases, which are baseline period, arterial transit and exchange period of labeled protons, and decayed period of labeled protons. PS = permeability surface area product

• 

  Fig. 4 Case of clinical application of perfusion MRI methods in patient with brain tumor. MR images and parameter maps (A) calculated from data of both dynamic susceptibility-contrast MRI (B), and dynamic contrast-enhanced MRI (C), obtained from patient who has abaplastic astrocytoma (World Health Organization grade III) in frontal lobe in brain. Brain-blood barrier is intact (CE T1WI), but tumor vascularity is increased. AUC = area under curve, CBF = cerebral blood flow, CBV = cerebral blood volume, CE T1WI = T1-weighted image after injecting contrast agent, FLAIR = fluid attenuated inversion recovery image, MTT = mean transit time, PE = peak enhancement, Pre-T1WI = T1-weighted image before injecting contrast agent, TTP = time-to-peak, T2WI = T2-weighted image

• 

  Fig. 5 Case of clinical application of arterial spin-labeling MRI in patient with brain infarction. Magnetic resonance images (A), and perfusion-weighted imaging (B), before (Pre-op) and after (Post-op) bypass surgery, in 59-year-old male with border zone infarction. A. Image shows DWI obtained with b-value of 1000 s/mm2, and corresponding ADC map, time-of-flight MRA, and CE MRA. High signal intensity on DWI at left side of brain indicates area with decreased diffusion, and MRA shows occlusion of middle cerebral artery. B. Image shows two slices of perfusion-weighted images before, and after bypass surgery. Slightly increased CBF is shown after bypass surgery. Only small amount of CBF is observed, because images were obtained immediately after bypass surgery. ADC = apparent diffusion coefficient, CBF = cerebral blood flow, CE MRA = magnetic resonance angiography with injecting contrast agent, DWI = diffusion-weighted imaging, MRA = magnetic resonance angiography with time-of-flight technique

Reference

1. Rosen BR, Belliveau JW, Vevea JM, Brady TJ. Perfusion imaging with NMR contrast agents. Magn Reson Med. 1990; 14:249–265.

2. Erlemann R, Reiser MF, Peters PE, Vasallo P, Nommensen B, Kusnierz-Glaz CR, et al. Musculoskeletal neoplasms: static and dynamic Gd-DTPA--enhanced MR imaging. Radiology. 1989; 171:767–773.

3. Detre JA, Leigh JS, Williams DS, Koretsky AP. Perfusion imaging. Magn Reson Med. 1992; 23:37–45.

4. Weisskoff RM, Zuo CS, Boxerman JL, Rosen BR. Microscopic susceptibility variation and transverse relaxation: theory and experiment. Magn Reson Med. 1994; 31:601–610.

5. Simonsen CZ, Ostergaard L, Vestergaard-Poulsen P, Røhl L, Bjørnerud A, Gyldensted C. CBF and CBV measurements by USPIO bolus tracking: reproducibility and comparison with Gd-based values. J Magn Reson Imaging. 1999; 9:342–347.

6. Stanisz GJ, Henkelman RM. Gd-DTPA relaxivity depends on macromolecular content. Magn Reson Med. 2000; 44:665–667.

7. Pintaske J, Martirosian P, Graf H, Erb G, Lodemann KP, Claussen CD, et al. Relaxivity of Gadopentetate Dimeglumine (Magnevist), Gadobutrol (Gadovist), and Gadobenate Dimeglumine (MultiHance) in human blood plasma at 0.2, 1.5, and 3 Tesla. Invest Radiol. 2006; 41:213–221.

8. Buckley DL, Kershaw LE, Stanisz GJ. Cellular-interstitial water exchange and its effect on the determination of contrast agent concentration in vivo: dynamic contrast-enhanced MRI of human internal obturator muscle. Magn Reson Med. 2008; 60:1011–1019.

9. Wong EC. An introduction to ASL labeling techniques. J Magn Reson Imaging. 2014; 40:1–10.

10. Williams DS, Detre JA, Leigh JS, Koretsky AP. Magnetic resonance imaging of perfusion using spin inversion of arterial water. Proc Natl Acad Sci U S A. 1992; 89:212–216.

11. Alsop DC, Detre JA. Multisection cerebral blood flow MR imaging with continuous arterial spin labeling. Radiology. 1998; 208:410–416.

12. Edelman RR, Siewert B, Darby DG, Thangaraj V, Nobre AC, Mesulam MM, et al. Qualitative mapping of cerebral blood flow and functional localization with echo-planar MR imaging and signal targeting with alternating radio frequency. Radiology. 1994; 192:513–520.

13. Kwong KK, Chesler DA, Weisskoff RM, Donahue KM, Davis TL, Ostergaard L, et al. MR perfusion studies with T1-weighted echo planar imaging. Magn Reson Med. 1995; 34:878–887.

14. Kim SG. Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion recovery (FAIR) technique: application to functional mapping. Magn Reson Med. 1995; 34:293–301.

15. Wong EC, Buxton RB, Frank LR. Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling. NMR Biomed. 1997; 10:237–249.

16. Pruessmann KP, Golay X, Stuber M, Scheidegger MB, Boesiger P. RF pulse concatenation for spatially selective inversion. J Magn Reson. 2000; 146:58–65.

17. Jahng GH, Zhu XP, Matson GB, Weiner MW, Schuff N. Improved perfusion-weighted MRI by a novel double inversion with proximal labeling of both tagged and control acquisitions. Magn Reson Med. 2003; 49:307–314.

18. Jahng GH, Weiner MW, Schuff N. Improved arterial spin labeling method: applications for measurements of cerebral blood flow in human brain at high magnetic field MRI. Med Phys. 2007; 34:4519–4525.

19. Wong EC, Cronin M, Wu WC, Inglis B, Frank LR, Liu TT. Velocity-selective arterial spin labeling. Magn Reson Med. 2006; 55:1334–1341.

20. Kiselev VG. On the theoretical basis of perfusion measurements by dynamic susceptibility contrast MRI. Magn Reson Med. 2001; 46:1113–1122.

21. Speck O, Chang L, DeSilva NM, Ernst T. Perfusion MRI of the human brain with dynamic susceptibility contrast: gradient-echo versus spin-echo techniques. J Magn Reson Imaging. 2000; 12:381–387.

22. Zhu XP, Li KL, Kamaly-Asl ID, Checkley DR, Tessier JJ, Waterton JC, et al. Quantification of endothelial permeability, leakage space, and blood volume in brain tumors using combined T1 and T2* contrast-enhanced dynamic MR imaging. J Magn Reson Imaging. 2000; 11:575–585.

23. Günther M, Bock M, Schad LR. Arterial spin labeling in combination with a look-locker sampling strategy: inflow turbo-sampling EPI-FAIR (ITS-FAIR). Magn Reson Med. 2001; 46:974–984.

24. Brookes MJ, Morris PG, Gowland PA, Francis ST. Noninvasive measurement of arterial cerebral blood volume using Look-Locker EPI and arterial spin labeling. Magn Reson Med. 2007; 58:41–54.

25. Francis ST, Bowtell R, Gowland PA. Modeling and optimization of Look-Locker spin labeling for measuring perfusion and transit time changes in activation studies taking into account arterial blood volume. Magn Reson Med. 2008; 59:316–325.

26. Fernández-Seara MA, Wang Z, Wang J, Rao HY, Guenther M, Feinberg DA, et al. Continuous arterial spin labeling perfusion measurements using single shot 3D GRASE at 3 T. Magn Reson Med. 2005; 54:1241–1247.

27. Günther M, Oshio K, Feinberg DA. Single-shot 3D imaging techniques improve arterial spin labeling perfusion measurements. Magn Reson Med. 2005; 54:491–498.

28. Talagala SL, Ye FQ, Ledden PJ, Chesnick S. Whole-brain 3D perfusion MRI at 3.0 T using CASL with a separate labeling coil. Magn Reson Med. 2004; 52:131–140.

29. Wong EC. New developments in arterial spin labeling pulse sequences. NMR Biomed. 2013; 26:887–891.

30. Calamante F, Vonken EJ, van Osch MJ. Contrast agent concentration measurements affecting quantification of bolus-tracking perfusion MRI. Magn Reson Med. 2007; 58:544–553.

31. Li KL, Buonaccorsi G, Thompson G, Cain JR, Watkins A, Russell D, et al. An improved coverage and spatial resolution--using dual injection dynamic contrast-enhanced (ICE-DICE) MRI: a novel dynamic contrast-enhanced technique for cerebral tumors. Magn Reson Med. 2012; 68:452–462.

32. Alsop DC, Detre JA, Golay X, Günther M, Hendrikse J, Hernandez-Garcia L, et al. Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med. 2014; doi: 10.1002/mrm.25197.

33. Meier P, Zierler KL. On the theory of the indicator-dilution method for measurement of blood flow and volume. J Appl Physiol. 1954; 6:731–744.

34. Ostergaard L, Weisskoff RM, Chesler DA, Gyldensted C, Rosen BR. High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis. Magn Reson Med. 1996; 36:715–725.

35. Thompson HK Jr, Starmer CF, Whalen RE, Mcintosh HD. Indicator transit time considered as a gamma variate. Circ Res. 1964; 14:502–515.

36. Wong EC, Buxton RB, Frank LR. Quantitative imaging of perfusion using a single subtraction (QUIPSS and QUIPSS II). Magn Reson Med. 1998; 39:702–708.

37. Luh WM, Wong EC, Bandettini PA, Hyde JS. QUIPSS II with thin-slice TI1 periodic saturation: a method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling. Magn Reson Med. 1999; 41:1246–1254.

38. Detre JA, Alsop DC, Vives LR, Maccotta L, Teener JW, Raps EC. Noninvasive MRI evaluation of cerebral blood flow in cerebrovascular disease. Neurology. 1998; 50:633–641.

39. Alsop DC, Detre JA. Reduced transit-time sensitivity in noninvasive magnetic resonance imaging of human cerebral blood flow. J Cereb Blood Flow Metab. 1996; 16:1236–1249.

40. Paulson OB, Hertz MM, Bolwig TG, Lassen NA. Water filtration and diffusion across the blood brain barrier in man. Acta Neurol Scand Suppl. 1977; 64:492–493.

41. Li KL, Zhu X, Hylton N, Jahng GH, Weiner MW, Schuff N. Four-phase single-capillary stepwise model for kinetics in arterial spin labeling MRI. Magn Reson Med. 2005; 53:511–518.

42. Starmer CF, Clark DO. Computer computations of cardiac output using the gamma function. J Appl Physiol. 1970; 28:219–220.

43. Weisskoff RM, Chesler D, Boxerman JL, Rosen BR. Pitfalls in MR measurement of tissue blood flow with intravascular tracers: which mean transit time? Magn Reson Med. 1993; 29:553–558.

44. Calamante F, Thomas DL, Pell GS, Wiersma J, Turner R. Measuring cerebral blood flow using magnetic resonance imaging techniques. J Cereb Blood Flow Metab. 1999; 19:701–735.

45. Calamante F, Gadian DG, Connelly A. Quantification of perfusion using bolus tracking magnetic resonance imaging in stroke: assumptions, limitations, and potential implications for clinical use. Stroke. 2002; 33:1146–1151.

46. Calamante F. Arterial input function in perfusion MRI: a comprehensive review. Prog Nucl Magn Reson Spectrosc. 2013; 74:1–32.

47. Rosen BR, Belliveau JW, Buchbinder BR, McKinstry RC, Porkka LM, Kennedy DN, et al. Contrast agents and cerebral hemodynamics. Magn Reson Med. 1991; 19:285–292.

48. Benner T, Heiland S, Erb G, Forsting M, Sartor K. Accuracy of gamma-variate fits to concentration-time curves from dynamic susceptibility-contrast enhanced MRI: influence of time resolution, maximal signal drop and signal-to-noise. Magn Reson Imaging. 1997; 15:307–317.

49. Wu Y, An H, Krim H, Lin W. An independent component analysis approach for minimizing effects of recirculation in dynamic susceptibility contrast magnetic resonance imaging. J Cereb Blood Flow Metab. 2007; 27:632–645.

50. Calamante F. Bolus dispersion issues related to the quantification of perfusion MRI data. J Magn Reson Imaging. 2005; 22:718–722.

51. Wirestam R, Andersson L, Ostergaard L, Bolling M, Aunola JP, Lindgren A, et al. Assessment of regional cerebral blood flow by dynamic susceptibility contrast MRI using different deconvolution techniques. Magn Reson Med. 2000; 43:691–700.

52. Calamante F, Gadian DG, Connelly A. Delay and dispersion effects in dynamic susceptibility contrast MRI: simulations using singular value decomposition. Magn Reson Med. 2000; 44:466–473.

53. Wu O, Østergaard L, Weisskoff RM, Benner T, Rosen BR, Sorensen AG. Tracer arrival timing-insensitive technique for estimating flow in MR perfusion-weighted imaging using singular value decomposition with a block-circulant deconvolution matrix. Magn Reson Med. 2003; 50:164–174.

54. Gall P, Emerich P, Kjølby BF, Kellner E, Mader I, Kiselev VG. On the design of filters for Fourier and oSVD-based deconvolution in bolus tracking perfusion MRI. MAGMA. 2010; 23:187–195.

55. Calamante F, Gadian DG, Connelly A. Quantification of bolus-tracking MRI: improved characterization of the tissue residue function using Tikhonov regularization. Magn Reson Med. 2003; 50:1237–1247.

56. Zanderigo F, Bertoldo A, Pillonetto G, Cobelli Ast C. Nonlinear stochastic regularization to characterize tissue residue function in bolus-tracking MRI: assessment and comparison with SVD, block-circulant SVD, and Tikhonov. IEEE Trans Biomed Eng. 2009; 56:1287–1297.

57. Vonken EJ, van Osch MJ, Bakker CJ, Viergever MA. Measurement of cerebral perfusion with dual-echo multi-slice quantitative dynamic susceptibility contrast MRI. J Magn Reson Imaging. 1999; 10:109–117.

58. Willats L, Connelly A, Calamante F. Minimising the effects of bolus dispersion in bolus-tracking MRI. NMR Biomed. 2008; 21:1126–1137.

59. Willats L, Connelly A, Calamante F. Improved deconvolution of perfusion MRI data in the presence of bolus delay and dispersion. Magn Reson Med. 2006; 56:146–156.

60. Grüner R, Taxt T. Iterative blind deconvolution in magnetic resonance brain perfusion imaging. Magn Reson Med. 2006; 55:805–815.

61. Mehndiratta A, Calamante F, Macintosh BJ, Crane DE, Payne SJ, Chappell MA. Modeling and correction of bolus dispersion effects in dynamic susceptibility contrast MRI. Magn Reson Med. 2014; doi: 10.1002/mrm.25077.

62. Mouridsen K, Friston K, Hjort N, Gyldensted L, Østergaard L, Kiebel S. Bayesian estimation of cerebral perfusion using a physiological model of microvasculature. Neuroimage. 2006; 33:570–579.

63. Kao YH, Guo WY, Wu YT, Liu KC, Chai WY, Lin CY, et al. Hemodynamic segmentation of MR brain perfusion images using independent component analysis, thresholding, and Bayesian estimation. Magn Reson Med. 2003; 49:885–894.

64. Kidwell CS, Saver JL, Mattiello J, Starkman S, Vinuela F, Duckwiler G, et al. Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging. Ann Neurol. 2000; 47:462–469.

65. Calamante F, Christensen S, Desmond PM, Ostergaard L, Davis SM, Connelly A. The physiological significance of the time-to-maximum (Tmax) parameter in perfusion MRI. Stroke. 2010; 41:1169–1174.

66. Tofts PS, Brix G, Buckley DL, Evelhoch JL, Henderson E, Knopp MV, et al. Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging. 1999; 10:223–232.

67. Jackson A, Li KL, Zhu X. Semi-quantitative parameter analysis of DCE-MRI revisited: monte-carlo simulation, clinical comparisons, and clinical validation of measurement errors in patients with type 2 neurofibromatosis. PLoS One. 2014; 9:e90300.

68. Tofts PS. Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging. 1997; 7:91–101.

69. St Lawrence KS, Lee TY. An adiabatic approximation to the tissue homogeneity model for water exchange in the brain: II. Experimental validation. J Cereb Blood Flow Metab. 1998; 18:1378–1385.

70. Brix G, Bahner ML, Hoffmann U, Horvath A, Schreiber W. Regional blood flow, capillary permeability, and compartmental volumes: measurement with dynamic CT--initial experience. Radiology. 1999; 210:269–276.

71. Larsson HB, Courivaud F, Rostrup E, Hansen AE. Measurement of brain perfusion, blood volume, and blood-brain barrier permeability, using dynamic contrast-enhanced T(1)-weighted MRI at 3 tesla. Magn Reson Med. 2009; 62:1270–1281.

72. Kety SS, Schmidt CF. The nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure and normal values. J Clin Invest. 1948; 27:476–483.

73. Buxton RB, Frank LR, Wong EC, Siewert B, Warach S, Edelman RR. A general kinetic model for quantitative perfusion imaging with arterial spin labeling. Magn Reson Med. 1998; 40:383–396.

74. Willats L, Calamante F. The 39 steps: evading error and deciphering the secrets for accurate dynamic susceptibility contrast MRI. NMR Biomed. 2013; 26:913–931.

75. Calamante F, Connelly A, van Osch MJ. Nonlinear DeltaR*2 effects in perfusion quantification using bolus-tracking MRI. Magn Reson Med. 2009; 61:486–492.

76. Calamante F, Willats L, Gadian DG, Connelly A. Bolus delay and dispersion in perfusion MRI: implications for tissue predictor models in stroke. Magn Reson Med. 2006; 55:1180–1185.

77. Calamante F, Yim PJ, Cebral JR. Estimation of bolus dispersion effects in perfusion MRI using image-based computational fluid dynamics. Neuroimage. 2003; 19(2 Pt 1):341–353.

78. Calamante F, Mørup M, Hansen LK. Defining a local arterial input function for perfusion MRI using independent component analysis. Magn Reson Med. 2004; 52:789–797.

79. Willats L, Christensen S, Ma HK, Donnan GA, Connelly A, Calamante F. Validating a local Arterial Input Function method for improved perfusion quantification in stroke. J Cereb Blood Flow Metab. 2011; 31:2189–2198.

80. Lorenz C, Benner T, Chen PJ, Lopez CJ, Ay H, Zhu MW, et al. Automated perfusion-weighted MRI using localized arterial input functions. J Magn Reson Imaging. 2006; 24:1133–1139.

81. van Osch MJ, Vonken EJ, Viergever MA, van der Grond J, Bakker CJ. Measuring the arterial input function with gradient echo sequences. Magn Reson Med. 2003; 49:1067–1076.

82. Bleeker EJ, van Buchem MA, van Osch MJ. Optimal location for arterial input function measurements near the middle cerebral artery in first-pass perfusion MRI. J Cereb Blood Flow Metab. 2009; 29:840–852.

83. Bleeker EJ, van Osch MJ, Connelly A, van Buchem MA, Webb AG, Calamante F. New criterion to aid manual and automatic selection of the arterial input function in dynamic susceptibility contrast MRI. Magn Reson Med. 2011; 65:448–456.

84. Bjornerud A, Sorensen AG, Mouridsen K, Emblem KE. T1- and T2*-dominant extravasation correction in DSC-MRI: part I--theoretical considerations and implications for assessment of tumor hemodynamic properties. J Cereb Blood Flow Metab. 2011; 31:2041–2053.

85. Boxerman JL, Hamberg LM, Rosen BR, Weisskoff RM. MR contrast due to intravascular magnetic susceptibility perturbations. Magn Reson Med. 1995; 34:555–566.

86. Shin W, Horowitz S, Ragin A, Chen Y, Walker M, Carroll TJ. Quantitative cerebral perfusion using dynamic susceptibility contrast MRI: evaluation of reproducibility and age- and gender-dependence with fully automatic image postprocessing algorithm. Magn Reson Med. 2007; 58:1232–1241.

87. Zaharchuk G, Straka M, Marks MP, Albers GW, Moseley ME, Bammer R. Combined arterial spin label and dynamic susceptibility contrast measurement of cerebral blood flow. Magn Reson Med. 2010; 63:1548–1556.

88. Bonekamp D, Degaonkar M, Barker PB. Quantitative cerebral blood flow in dynamic susceptibility contrast MRI using total cerebral flow from phase contrast magnetic resonance angiography. Magn Reson Med. 2011; 66:57–66.

89. Parker GJ, Baustert I, Tanner SF, Leach MO. Improving image quality and T(1) measurements using saturation recovery turboFLASH with an approximate K-space normalisation filter. Magn Reson Imaging. 2000; 18:157–167.

90. Buckley DL. Uncertainty in the analysis of tracer kinetics using dynamic contrast-enhanced T1-weighted MRI. Magn Reson Med. 2002; 47:601–606.

91. Landis CS, Li X, Telang FW, Coderre JA, Micca PL, Rooney WD, et al. Determination of the MRI contrast agent concentration time course in vivo following bolus injection: effect of equilibrium transcytolemmal water exchange. Magn Reson Med. 2000; 44:563–574.

92. Silver MS, Joseph RI, Hoult DI. Selective spin inversion in nuclear magnetic resonance and coherent optics through an exact solution of the Bloch-Riccati equation. Phys Rev A. 1985; 31:2753–2755.

93. Ordidge RJ, Wylezinska M, Hugg JW, Butterworth E, Franconi F. Frequency offset corrected inversion (FOCI) pulses for use in localized spectroscopy. Magn Reson Med. 1996; 36:562–566.

94. Warnking JM, Pike GB. Bandwidth-modulated adiabatic RF pulses for uniform selective saturation and inversion. Magn Reson Med. 2004; 52:1190–1199.

95. Dixon WT, Sardashti M, Castillo M, Stomp GP. Multiple inversion recovery reduces static tissue signal in angiograms. Magn Reson Med. 1991; 18:257–268.

96. Ye FQ, Frank JA, Weinberger DR, McLaughlin AC. Noise reduction in 3D perfusion imaging by attenuating the static signal in arterial spin tagging (ASSIST). Magn Reson Med. 2000; 44:92–100.

97. Alsop DC. Arterial spin labeling: its time is now. MAGMA. 2012; 25:75–77.

98. Jahng GH, Stables L, Ebel A, Matson GB, Meyerhoff DJ, Weiner MW, et al. Sensitive and fast T1 mapping based on two inversion recovery images and a reference image. Med Phys. 2005; 32:1524–1528.

99. Yang Y, Engelien W, Xu S, Gu H, Silbersweig DA, Stern E. Transit time, trailing time, and cerebral blood flow during brain activation: measurement using multislice, pulsed spin-labeling perfusion imaging. Magn Reson Med. 2000; 44:680–685.

100. Gonzalez-At JB, Alsop DC, Detre JA. Cerebral perfusion and arterial transit time changes during task activation determined with continuous arterial spin labeling. Magn Reson Med. 2000; 43:739–746.

101. Chen Y, Wang DJ, Detre JA. Comparison of arterial transit times estimated using arterial spin labeling. MAGMA. 2012; 25:135–144.

102. Asllani I, Borogovac A, Brown TR. Regression algorithm correcting for partial volume effects in arterial spin labeling MRI. Magn Reson Med. 2008; 60:1362–1371.

103. Liang X, Connelly A, Calamante F. Improved partial volume correction for single inversion time arterial spin labeling data. Magn Reson Med. 2013; 69:531–537.

104. Chappell MA, Groves AR, MacIntosh BJ, Donahue MJ, Jezzard P, Woolrich MW. Partial volume correction of multiple inversion time arterial spin labeling MRI data. Magn Reson Med. 2011; 65:1173–1183.

105. Kiselev VG. Transverse relaxation effect of MRI contrast agents: a crucial issue for quantitative measurements of cerebral perfusion. J Magn Reson Imaging. 2005; 22:693–696.

106. Bleeker EJ, van Buchem MA, Webb AG, van Osch MJ. Phase-based arterial input function measurements for dynamic susceptibility contrast MRI. Magn Reson Med. 2010; 64:358–368.

107. Straka M, Albers GW, Bammer R. Real-time diffusion-perfusion mismatch analysis in acute stroke. J Magn Reson Imaging. 2010; 32:1024–1037.

108. Kim J, Leira EC, Callison RC, Ludwig B, Moritani T, Magnotta VA, et al. Toward fully automated processing of dynamic susceptibility contrast perfusion MRI for acute ischemic cerebral stroke. Comput Methods Programs Biomed. 2010; 98:204–213.

109. Bjørnerud A, Emblem KE. A fully automated method for quantitative cerebral hemodynamic analysis using DSC-MRI. J Cereb Blood Flow Metab. 2010; 30:1066–1078.

110. Dai W, Garcia D, de Bazelaire C, Alsop DC. Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields. Magn Reson Med. 2008; 60:1488–1497.

111. Garcia DM, Duhamel G, Alsop DC. Efficiency of inversion pulses for background suppressed arterial spin labeling. Magn Reson Med. 2005; 54:366–372.

112. Zaharchuk G, Ledden PJ, Kwong KK, Reese TG, Rosen BR, Wald LL. Multislice perfusion and perfusion territory imaging in humans with separate label and image coils. Magn Reson Med. 1999; 41:1093–1098.

113. Paiva FF, Tannús A, Talagala SL, Silva AC. Arterial spin labeling of cerebral perfusion territories using a separate labeling coil. J Magn Reson Imaging. 2008; 27:970–977.

114. Helle M, Rüfer S, Alfke K, Jansen O, Norris DG. Perfusion territory imaging of intracranial branching arteries - optimization of continuous artery-selective spin labeling (CASSL). NMR Biomed. 2011; 24:404–412.

115. Davies NP, Jezzard P. Selective arterial spin labeling (SASL): perfusion territory mapping of selected feeding arteries tagged using two-dimensional radiofrequency pulses. Magn Reson Med. 2003; 49:1133–1142.

116. Hendrikse J, van der Grond J, Lu H, van Zijl PC, Golay X. Flow territory mapping of the cerebral arteries with regional perfusion MRI. Stroke. 2004; 35:882–887.

117. Zimine I, Petersen ET, Golay X. Dual vessel arterial spin labeling scheme for regional perfusion imaging. Magn Reson Med. 2006; 56:1140–1144.

118. Günther M. Efficient visualization of vascular territories in the human brain by cycled arterial spin labeling MRI. Magn Reson Med. 2006; 56:671–675.

119. Wong EC. Vessel-encoded arterial spin-labeling using pseudocontinuous tagging. Magn Reson Med. 2007; 58:1086–1091.

120. Chappell MA, Okell TW, Jezzard P, Woolrich MW. A general framework for the analysis of vessel encoded arterial spin labeling for vascular territory mapping. Magn Reson Med. 2010; 64:1529–1539.

121. Helle M, Norris DG, Rüfer S, Alfke K, Jansen O, van Osch MJ. Superselective pseudocontinuous arterial spin labeling. Magn Reson Med. 2010; 64:777–786.

122. Hartkamp NS, Petersen ET, De Vis JB, Bokkers RP, Hendrikse J. Mapping of cerebral perfusion territories using territorial arterial spin labeling: techniques and clinical application. NMR Biomed. 2013; 26:901–912.

123. Larkman DJ, Hajnal JV, Herlihy AH, Coutts GA, Young IR, Ehnholm G. Use of multicoil arrays for separation of signal from multiple slices simultaneously excited. J Magn Reson Imaging. 2001; 13:313–317.

124. Feinberg DA, Beckett A, Chen L. Arterial spin labeling with simultaneous multi-slice echo planar imaging. Magn Reson Med. 2013; 70:1500–1506.

125. Kim T, Shin W, Zhao T, Beall EB, Lowe MJ, Bae KT. Whole brain perfusion measurements using arterial spin labeling with multiband acquisition. Magn Reson Med. 2013; 70:1653–1661.

126. Dixon WT, Du LN, Faul DD, Gado M, Rossnick S. Projection angiograms of blood labeled by adiabatic fast passage. Magn Reson Med. 1986; 3:454–462.

127. Robson PM, Dai W, Shankaranarayanan A, Rofsky NM, Alsop DC. Time-resolved vessel-selective digital subtraction MR angiography of the cerebral vasculature with arterial spin labeling. Radiology. 2010; 257:507–515.

128. Petersen ET, Lim T, Golay X. Model-free arterial spin labeling quantification approach for perfusion MRI. Magn Reson Med. 2006; 55:219–232.

129. Silva AC, Williams DS, Koretsky AP. Evidence for the exchange of arterial spin-labeled water with tissue water in rat brain from diffusion-sensitized measurements of perfusion. Magn Reson Med. 1997; 38:232–237.

130. Saver JL. Time is brain--quantified. Stroke. 2006; 37:263–266.

131. Covarrubias DJ, Rosen BR, Lev MH. Dynamic magnetic resonance perfusion imaging of brain tumors. Oncologist. 2004; 9:528–537.

132. Waldman AD, Jackson A, Price SJ, Clark CA, Booth TC, Auer DP, et al. Quantitative imaging biomarkers in neuro-oncology. Nat Rev Clin Oncol. 2009; 6:445–454.

133. Sourbron S, Ingrisch M, Siefert A, Reiser M, Herrmann K. Quantification of cerebral blood flow, cerebral blood volume, and blood-brain-barrier leakage with DCE-MRI. Magn Reson Med. 2009; 62:205–217.

134. Moody AR, Martel A, Kenton A, Allder S, Horsfield MA, Delay G, et al. Contrast-reduced imaging of tissue concentration and arterial level (CRITICAL) for assessment of cerebral hemodynamics in acute stroke by magnetic resonance. Invest Radiol. 2000; 35:401–411.

135. Martel AL, Allder SJ, Delay GS, Morgan PS, Moody AA. Perfusion MRI of infarcted and noninfarcted brain tissue in stroke: a comparison of conventional hemodynamic imaging and factor analysis of dynamic studies. Invest Radiol. 2001; 36:378–385.

136. Singh A, Haris M, Rathore D, Purwar A, Sarma M, Bayu G, et al. Quantification of physiological and hemodynamic indices using T(1) dynamic contrast-enhanced MRI in intracranial mass lesions. J Magn Reson Imaging. 2007; 26:871–880.

137. Larsson HB, Hansen AE, Berg HK, Rostrup E, Haraldseth O. Dynamic contrast-enhanced quantitative perfusion measurement of the brain using T1-weighted MRI at 3T. J Magn Reson Imaging. 2008; 27:754–762.

138. Leigh R, Jen SS, Varma DD, Hillis AE, Barker PB. Arrival time correction for dynamic susceptibility contrast MR permeability imaging in stroke patients. PLoS One. 2012; 7:e52656.

139. Law M, Yang S, Babb JS, Knopp EA, Golfinos JG, Zagzag D, et al. Comparison of cerebral blood volume and vascular permeability from dynamic susceptibility contrast-enhanced perfusion MR imaging with glioma grade. AJNR Am J Neuroradiol. 2004; 25:746–755.

140. Kim EJ, Kim DH, Lee SH, Huh YM, Song HT, Suh JS. Simultaneous acquisition of perfusion and permeability from corrected relaxation rates with dynamic susceptibility contrast dual gradient echo. Magn Reson Imaging. 2004; 22:307–314.

141. Provenzale JM, Wang GR, Brenner T, Petrella JR, Sorensen AG. Comparison of permeability in high-grade and low-grade brain tumors using dynamic susceptibility contrast MR imaging. AJR Am J Roentgenol. 2002; 178:711–716.

142. Larsson HB, Stubgaard M, Frederiksen JL, Jensen M, Henriksen O, Paulson OB. Quantitation of blood-brain barrier defect by magnetic resonance imaging and gadolinium-DTPA in patients with multiple sclerosis and brain tumors. Magn Reson Med. 1990; 16:117–131.

143. Tofts PS, Kermode AG. Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med. 1991; 17:357–367.

144. Materne R, Smith AM, Peeters F, Dehoux JP, Keyeux A, Horsmans Y, et al. Assessment of hepatic perfusion parameters with dynamic MRI. Magn Reson Med. 2002; 47:135–142.

145. Choyke PL, Dwyer AJ, Knopp MV. Functional tumor imaging with dynamic contrast-enhanced magnetic resonance imaging. J Magn Reson Imaging. 2003; 17:509–520.

146. Jerosch-Herold M, Seethamraju RT, Swingen CM, Wilke NM, Stillman AE. Analysis of myocardial perfusion MRI. J Magn Reson Imaging. 2004; 19:758–770.

147. Brix G, Kiessling F, Lucht R, Darai S, Wasser K, Delorme S, et al. Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series. Magn Reson Med. 2004; 52:420–429.

148. Dujardin M, Sourbron S, Luypaert R, Verbeelen D, Stadnik T. Quantification of renal perfusion and function on a voxel-by-voxel basis: a feasibility study. Magn Reson Med. 2005; 54:841–849.

149. Pandharipande PV, Krinsky GA, Rusinek H, Lee VS. Perfusion imaging of the liver: current challenges and future goals. Radiology. 2005; 234:661–673.

150. Kershaw LE, Hutchinson CE, Buckley DL. Benign prostatic hyperplasia: evaluation of T1, T2, and microvascular characteristics with T1-weighted dynamic contrast-enhanced MRI. J Magn Reson Imaging. 2009; 29:641–648.

151. Kim SM, Kim MJ, Rhee HY, Ryu CW, Kim EJ, Petersen ET, et al. Regional cerebral perfusion in patients with Alzheimer's disease and mild cognitive impairment: effect of APOE epsilon4 allele. Neuroradiology. 2013; 55:25–34.

152. Du AT, Jahng GH, Hayasaka S, Kramer JH, Rosen HJ, Gorno-Tempini ML, et al. Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI. Neurology. 2006; 67:1215–1220.

153. Hayasaka S, Du AT, Duarte A, Kornak J, Jahng GH, Weiner MW, et al. A non-parametric approach for co-analysis of multi-modal brain imaging data: application to Alzheimer's disease. Neuroimage. 2006; 30:768–779.

154. Johnson NA, Jahng GH, Weiner MW, Miller BL, Chui HC, Jagust WJ, et al. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience. Radiology. 2005; 234:851–859.

155. Bokkers RP, van Osch MJ, Klijn CJ, Kappelle LJ, Hendrikse J. Cerebrovascular reactivity within perfusion territories in patients with an internal carotid artery occlusion. J Neurol Neurosurg Psychiatry. 2011; 82:1011–1016.

156. Song YS, Choi SH, Park CK, Yi KS, Lee WJ, Yun TJ, et al. True progression versus pseudoprogression in the treatment of glioblastomas: a comparison study of normalized cerebral blood volume and apparent diffusion coefficient by histogram analysis. Korean J Radiol. 2013; 14:662–672.

157. Choi YJ, Kim HS, Jahng GH, Kim SJ, Suh DC. Pseudoprogression in patients with glioblastoma: added value of arterial spin labeling to dynamic susceptibility contrast perfusion MR imaging. Acta Radiol. 2013; 54:448–454.

158. Haller S, Rodriguez C, Moser D, Toma S, Hofmeister J, Sinanaj I, et al. Acute caffeine administration impact on working memory-related brain activation and functional connectivity in the elderly: a BOLD and perfusion MRI study. Neuroscience. 2013; 250:364–371.

159. Liang X, Tournier JD, Masterton R, Connelly A, Calamante F. A k-space sharing 3D GRASE pseudocontinuous ASL method for whole-brain resting-state functional connectivity. Int J Imaging Syst Technol. 2012; 22:37–43.

160. Liang X, Connelly A, Calamante F. Graph analysis of resting-state ASL perfusion MRI data: nonlinear correlations among CBF and network metrics. Neuroimage. 2014; 87:265–275.