Abstract
Dynamic contrast-enhanced computed tomography (DCE-CT) and magnetic resonance imaging (DCE-MRI) are functional imaging techniques. They aim to characterise the microcirculation by applying the principles of tracer-kinetic analysis to concentration–time curves measured in individual image pixels. In this paper, we review the basic principles of DCE-MRI and DCE-CT, with a specific emphasis on the use of tracer-kinetic modeling. The aim is to provide an introduction to the field for a broader audience of pharmacokinetic modelers. In a first part, we first review the key aspects of data acquisition in DCE-CT and DCE-MRI, including a review of basic measurement strategies, a discussion on the relation between signal and concentration, and the problem of measuring reference data in arterial blood. In a second part, we define the four main parameters that can be measured with these techniques and review the most common tracer-kinetic models that are used in this field. We first discuss the models for the capillary bed and then define the most general four-parameter models used today: the two-compartment exchange model, the tissue-homogeneity model, the “adiabatic approximation to the tissue-homogeneity model” and the distributed-parameter model. In simpler tissue types or when the data quality is inadequate to resolve all the features of the more complex models, it is often necessary to resort to simpler models, which are special cases of the general models and hence have less parameters. We discuss the most common of these special cases, i.e. the uptake models, the extended Tofts model, and the one-compartment model. Models for two specific tissue types, liver and kidney, are discussed separately. We conclude with a review of practical aspects of DCE-CT and DCE-MRI data analysis, including the problem of identifying a suitable model for any given data set, and a brief discussion of the application of tracer-kinetic modeling in the context of drug development. Here, an important application of DCE techniques is the derivation of quantitative imaging biomarkers for the assessment of effects of targeted therapeutics on tumors.
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Ahearn TS, Staff RT, Redpath TW, Semple SIK (2005) The use of the Levenberg–Marquardt curve-fitting algorithm in pharmacokinetic modelling of DCE-MRI data. Phys Med Biol 50(9):N85–N92
Allmendinger AM, Tang ER, Lui YW, Spektor V (2012) Imaging of stroke: part 1, perfusion CT—overview of imaging technique, interpretation pearls, and common pitfalls. AJR Am J Roentgenol 198(1):52–62
Annet L, Hermoye L, Peeters F, Jamar F, Dehoux JP, Beers BV (2004) Glomerular filtration rate: assessment with dynamic contrast-enhanced MRI and a cortical-compartment model in the rabbit kidney. J Magn Reson Imaging 20(5):843–849
Bains LJ, McGrath DM, Naish JH, Cheung S, Watson Y, Taylor MB, Logue JP, Parker GJM, Waterton JC, Buckley DL (2010) Tracer kinetic analysis of dynamic contrast-enhanced MRI and CT bladder cancer data: a preliminary comparison to assess the magnitude of water exchange effects. Magn Reson Med 64(2):595–603
Bamberg F, Becker A, Schwarz F, Marcus RP, Greif M, von Ziegler F, Blankstein R, Hoffmann U, Sommer WH, Hoffmann VS, Johnson TRC, Becker HCR, Wintersperger BJ, Reiser MF, Nikolaou K (2011) Detection of hemodynamically significant coronary artery stenosis: incremental diagnostic value of dynamic CT-based myocardial perfusion imaging. Radiology 260(3):689–698
Baumann D, Rudin M (2000) Quantitative assessment of rat kidney function by measuring the clearance of the contrast agent Gd(DOTA) using dynamic MRI. Magn Reson Imaging 18(5):587–595
Bauner KU, Sourbron S, Picciolo M, Schmitz C, Theisen D, Sandner TA, Reiser MF, Huber AM (2012) MR first pass perfusion of benign and malignant cardiac tumours-significant differences and diagnostic accuracy. Eur Radiol 22(1):73–82
Bellomi M, Petralia G, Sonzogni A, Zampino MG, Rocca A (2007) CT perfusion for the monitoring of neoadjuvant chemotherapy and radiation therapy in rectal carcinoma: initial experience. Radiology 244(2):486–493
Bisdas S, Baghi M, Wagenblast J, Vogl TJ, Thng CH, Koh TS (2008a) Gadolinium-enhanced echo-planar T2-weighted MRI of tumors in the extracranial head and neck: feasibility study and preliminary results using a distributed-parameter tracer kinetic analysis. J Magn Reson Imaging 27(5):963–969
Bisdas S, Donnerstag F, Berding G, Vogl TJ, Thng CH, Koh TS (2008b) Computed tomography assessment of cerebral perfusion using a distributed parameter tracer kinetics model: validation with H(2)((15))O positron emission tomography measurements and initial clinical experience in patients with acute stroke. J Cereb Blood Flow Metab 28(2):402–411
Bokacheva L, Rusinek H, Zhang J, Chen Q, Lee V (2009) Estimates of glomerular filtration rate from MR renography and tracer kinetic models. J Magn Reson Imaging 29(2):371–382
Brix G, Griebel J, Delorme S (2012) Dynamic contrast-enhanced computed tomography. Tracer kinetics and radiation hygienic principles. Radiologe 52(3):277–94; quiz 295–6
Brix G, Kiessling F, Lucht R, Darai S, Wasser K, Delorme S, Griebel J (2004) Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series. Magn Reson Med 52(2):420–429
Brix G, Zwick S, Kiessling F, Griebel J (2009) Pharmacokinetic analysis of tissue microcirculation using nested models: multimodel inference and parameter identifiability. Med Phys 36(7):2923–2933
Brix G, Griebel J, Kiessling F, Wenz F (2010) Tracer kinetic modelling of tumour angiogenesis based on dynamic contrast-enhanced CT and MRI measurements. Eur J Nucl Med Mol Imaging 37(Suppl 1):S30–S51
Brix G, Lechel U, Petersheim M, Krissak R, Fink C (2011) Dynamic contrast-enhanced CT studies: balancing patient exposure and image noise. Invest Radiol 46(1):64–70
Broadbent DA, Biglands JD, Larghat A, Sourbron SP, Radjenovic A, Greenwood JP, Plein S, Buckley DL (2013) Myocardial blood flow at rest and stress measured with dynamic contrast-enhanced MRI: comparison of a distributed parameter model with a fermi function model. Magn Reson Med. doi: 10.1002/mrm.24611
Buckley DL, Roberts C, Parker GJM, Logue JP, Hutchinson CE (2004) Prostate cancer: evaluation of vascular characteristics with dynamic contrast-enhanced T1-weighted MR imaging—initial experience. Radiology 233(3):709–715
Buckley D, Shurrab A, Cheung C, Jones A, Mamtora H, Kalra P (2006) Measurement of single kidney function using dynamic contrast-enhanced MRI: comparison of two models in human subjects. J Magn Reson Imaging 24(5):1117–1123
Buckley DL, Kershaw LE, Stanisz GJ (2008) 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 60(5):1011–1019
Burnham KP, Anderson DR (2002) Model selection and multimodel inference: a practical information-theoretic approach. Springer, New York
Calamante F, Gadian DG, Connelly A (2000) Delay and dispersion effects in dynamic susceptibility contrast MRI: simulations using singular value decomposition. Magn Reson Med 44(3):466–473
Cao Y, Tsien CI, Sundgren PC, Nagesh V, Normolle D, Buchtel H, Junck L, Lawrence TS (2009) Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for prediction of radiation-induced neurocognitive dysfunction. Clin Cancer Res 15(5):1747–1754
Cheong LHD, Lim CCT, Koh TS (2004) Dynamic contrast-enhanced CT of intracranial meningioma: comparison of distributed and compartmental tracer kinetic models—initial results. Radiology 232(3):921–930
Christian TF, Rettmann DW, Aletras AH, Liao SL, Taylor JL, Balaban RS, Arai AE (2004) Absolute myocardial perfusion in canines measured by using dual-bolus first-pass MR imaging. Radiology 232(3):677–684
Christian TF, Aletras AH, Arai AE (2008) Estimation of absolute myocardial blood flow during first-pass MR perfusion imaging using a dual-bolus injection technique: comparison to single-bolus injection method. J Magn Reson Imaging 27(6):1271–1277
Christian TF, Bell SP, Whitesell L, Jerosch-Herold M (2009) Accuracy of cardiac magnetic resonance of absolute myocardial blood flow with a high-field system: comparison with conventional field strength. JACC Cardiovasc Imaging 2(9):1103–1110
Covarrubias DJ, Rosen BR, Lev MH (2004) Dynamic magnetic resonance perfusion imaging of brain tumors. Oncologist 9(5):528–537
Cyran CC, von Einem JC, Paprottka PM, Schwarz B, Ingrisch M, Dietrich O, Hinkel R, Bruns CJ, Clevert DA, Eschbach R, Reiser MF, Wintersperger BJ, Nikolaou K (2012) Dynamic contrast-enhanced computed tomography imaging biomarkers correlated with immunohistochemistry for monitoring the effects of sorafenib on experimental prostate carcinomas. Invest Radiol 47(1):49–57
de Bazelaire C, Siauve N, Fournier L, Frouin F, Robert P, Clement O, de Kerviler E, Cuenod CA (2005) Comprehensive model for simultaneous MRI determination of perfusion and permeability using a blood-pool agent in rats rhabdomyosarcoma. Eur Radiol 15(12):2497–2505
Donaldson SB, Buckley DL, O’Connor JP, Davidson SE, Carrington BM, Jones AP, West CML (2010a) Enhancing fraction measured using dynamic contrast-enhanced MRI predicts disease-free survival in patients with carcinoma of the cervix. Br J Cancer 102(1):23–26
Donaldson SB, West CML, Davidson SE, Carrington BM, Hutchison G, Jones AP, Sourbron SP, Buckley DL (2010b) A comparison of tracer kinetic models for T1-weighted dynamic contrast-enhanced MRI: application in carcinoma of the cervix. Magn Reson Med 63(3):691–700
Ewing JR, Knight RA, Nagaraja TN, Yee JS, Nagesh V, Whitton PA, Li L, Fenstermacher JD (2003) Patlak plots of Gd-DTPA MRI data yield blood-brain transfer constants concordant with those of 14C-sucrose in areas of blood-brain opening. Magn Reson Med 50(2):283–292
Ferrier MC, Sarin H, Fung SH, Schatlo B, Pluta RM, Gupta SN, Choyke PL, Oldfield EH, Thomasson D, Butman JA (2007) Validation of dynamic contrast-enhanced magnetic resonance imaging-derived vascular permeability measurements using quantitative autoradiography in the RG2 rat brain tumor model. Neoplasia 9(7):546–555
Fink C, Ley S, Kroeker R, Requardt M, Kauczor HU, Bock M (2005) Time-resolved contrast-enhanced three-dimensional magnetic resonance angiography of the chest: combination of parallel imaging with view sharing (TREAT). Invest Radiol 40(1):40–48
Galbraith SM (2006) MR in oncology drug development. NMR Biomed 19(6):681–689
Garpebring A, Ostlund N, Karlsson M (2009) A novel estimation method for physiological parameters in dynamic contrast-enhanced MRI: application of a distributed parameter model using Fourier-domain calculations. IEEE Trans Med Imaging 28(9):1375–1383
Glatting G, Kletting P, Reske SN, Hohl K, Ring C (2007) Choosing the optimal fit function: comparison of the Akaike information criterion and the F-test. Med Phys 34(11):4285–4292
Goh V, Halligan S, Bartram CI (2007) Quantitative tumor perfusion assessment with multidetector CT: are measurements from two commercial software packages interchangeable? Radiology 242(3):777–782
Greis C (2011) Quantitative evaluation of microvascular blood flow by contrast-enhanced ultrasound (CEUS). Clin Hemorheol Microcirc 49(1–4):137–149
Gutin PH, Iwamoto FM, Beal K, Mohile NA, Karimi S, Hou BL, Lymberis S, Yamada Y, Chang J, Abrey LE (2009) Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol Biol Phys 75(1):156–163
Hahn OM, Yang C, Medved M, Karczmar G, Kistner E, Karrison T, Manchen E, Mitchell M, Ratain MJ, Stadler WM (2008) Dynamic contrast-enhanced magnetic resonance imaging pharmacodynamic biomarker study of sorafenib in metastatic renal carcinoma. J Clin Oncol 26(28):4572–4578
Hansen A, Pedersen H, Rostrup E, Larsson H (2009) Partial volume effect (PVE) on the arterial input function (AIF) in T1-weighted perfusion imaging and limitations of the multiplicative rescaling approach. Magn Reson Med 62(4):1055–1059
Haroon HA, Buckley DL, Patankar TA, Dow GR, Rutherford SA, Balriaux D, Jackson A (2004) A comparison of Ktrans measurements obtained with conventional and first pass pharmacokinetic models in human gliomas. J Magn Reson Imaging 19(5):527–536
Hsu LY, Rhoads KL, Holly JE, Kellman P, Aletras AH, Arai AE (2006) Quantitative myocardial perfusion analysis with a dual-bolus contrast-enhanced first-pass MRI technique in humans. J Magn Reson Imaging 23(3):315–322
Huber A, Sourbron S, Klauss V, Schaefer J, Bauner KU, Schweyer M, Reiser M, Rummeny E, Rieber J (2012) Magnetic resonance perfusion of the myocardium: semiquantitative and quantitative evaluation in comparison with coronary angiography and fractional flow reserve. Invest Radiol 47(6):332–338
Ingrisch M, Sourbron S, Reiser MF, Peller M (2010) Model selection in dynamic contrast enhanced MRI: the Akaike information criterion. In: Magjarevic R, Dössel O, Schlegel WC (eds) World congress on medical physics and biomedical engineering, IFMBE proceedings, vol 25/4. Springer, Berlin, pp 356–358
Ingrisch M, Dietrich O, Attenberger UI, Nikolaou K, Sourbron S, Reiser MF, Fink C (2010) Quantitative pulmonary perfusion magnetic resonance imaging: influence of temporal resolution and signal-to-noise ratio. Invest Radiol 45(1):7–14
Ingrisch M, Sourbron S, Morhard D, Ertl-Wagner B, Kümpfel T, Hohlfeld R, Reiser M, Glaser C (2012) Quantification of perfusion and permeability in multiple sclerosis: dynamic contrast-enhanced MRI in 3D at 3T. Invest Radiol 47(4):252–258
Ito H, Kanno I, Kato C, Sasaki T, Ishii K, Ouchi Y, Iida A, Okazawa H, Hayashida K, Tsuyuguchi N, et al (2004) Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15 O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan. Eur J Nuclear Med Mol Imaging 31(5):635–643
Ivancevic M, Zimine I, Foxall D, Lecoq G, Righetti A, Didier D, Vallée JP (2003) Inflow effect in first-pass cardiac and renal MRI. J Magn Reson Imaging 18(3):372–376
Jackson A, O’Connor JPB, Parker GJM, Jayson GC (2007) Imaging tumor vascular heterogeneity and angiogenesis using dynamic contrast-enhanced magnetic resonance imaging. Clin Cancer Res 13(12):3449–3459
Jacquez JA (1985) Compartmental analysis in biology and medicine. University of Michigan Press, Michigan
Jerosch-Herold M, Wilke N, Stillman AE (1998) Magnetic resonance quantification of the myocardial perfusion reserve with a Fermi function model for constrained deconvolution. Med Phys 25(1):73–84
Kermode AG, Thompson AJ, Tofts P, MacManus DG, Kendall BE, Kingsley DP, Moseley IF, Rudge P, McDonald WI (1990) Breakdown of the blood–brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain 113(Pt 5):1477–1489
Kermode AG, Tofts PS, Thompson AJ, MacManus DG, Rudge P, Kendall BE, Kingsley DP, Moseley IF, du Boulay EP, McDonald WI (1990) Heterogeneity of blood–brain barrier changes in multiple sclerosis: an MRI study with gadolinium-DTPA enhancement. Neurology 40(2):229–235
Kershaw LE, Buckley DL (2006) Precision in measurements of perfusion and microvascular permeability with T1-weighted dynamic contrast-enhanced MRI. Magn Reson Med 56(5):986–992
Kershaw LE, Hutchinson CE, Buckley DL (2009) Benign prostatic hyperplasia: evaluation of T1, T2, and microvascular characteristics with T1-weighted dynamic contrast-enhanced MRI. J Magn Reson Imaging 29(3):641–648
Knutsson L, Ståhlberg F, Wirestam R (2010) Absolute quantification of perfusion using dynamic susceptibility contrast MRI: pitfalls and possibilities. MAGMA 23(1):1–21
Koh TS, Zhang JL, Ong CK, Shuter B (2006) A biphasic parameter estimation method for quantitative analysis of dynamic renal scintigraphic data. Phys Med Biol 51(11):2857–2870
Koh TS, Thng CH, Lee PS, Hartono S, Rumpel H, Goh BC, Bisdas S (2008) Hepatic metastases: in vivo assessment of perfusion parameters at dynamic contrast-enhanced MR imaging with dual-input two-compartment tracer kinetics model. Radiology 249(1):307–320
Koh TS, Bisdas S, Koh DM, Thng CH (2011a) Fundamentals of tracer kinetics for dynamic contrast-enhanced MRI. J Magn Reson Imaging 34(6):1262–1276
Koh TS, Thng CH, Hartono S, Kwek JW, Khoo JBK, Miyazaki K, Collins DJ, Orton MR, Leach MO, Lewington V, Koh DM (2011b) Dynamic contrast-enhanced MRI of neuroendocrine hepatic metastases: a feasibility study using a dual-input two-compartment model. Magn Reson Med 65(1):250–260
Koh TS, Thng CH, Hartono S, Tai BC, Rumpel H, Ong AB, Sukri N, Soo RA, Wong CI, Low ASC, Humerickhouse RA, Goh BC (2011c) A comparative study of dynamic contrast-enhanced MRI parameters as biomarkers for anti-angiogenic drug therapy. NMR Biomed 24(9):1169–1180
Korporaal JG, van Vulpen M, van den Berg CAT, van der Heide UA (2012) Tracer kinetic model selection for dynamic contrast-enhanced computed tomography imaging of prostate cancer. Invest Radiol 47(1):41–48
Köstler H, Ritter C, Lipp M, Beer M, Hahn D, Sandstede J (2004) Prebolus quantitative MR heart perfusion imaging. Magn Reson Med 52(2):296–299
Landis CS, Li X, Telang FW, Coderre JA, Micca PL, Rooney WD, Latour LL, Vétek G, Pályka I, Springer CS (2000) Determination of the MRI contrast agent concentration time course in vivo following bolus injection: effect of equilibrium transcytolemmal water exchange. Magn Reson Med 44(4):563–574
Larsson HB, Rosenbaum S, Fritz-Hansen T (2001) Quantification of the effect of water exchange in dynamic contrast MRI perfusion measurements in the brain and heart. Magn Reson Med 46(2):272–281
Larsson HBW, Courivaud F, Rostrup E, Hansen AE (2009) 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 62(5):1270–1281
Lassen N, Perl W (1979) Tracer kinetic methods in medical physiology. Raven Press, New York
Lavini C, Verhoeff JJC (2010) Reproducibility of the gadolinium concentration measurements and of the fitting parameters of the vascular input function in the superior sagittal sinus in a patient population. Magn Reson Imaging 28(10):1420–1430
Lawrence KSS, Lee TY (1998) An adiabatic approximation to the tissue homogeneity model for water exchange in the brain: II. Experimental validation. J Cereb Blood Flow Metab 18(12):1378–1385
Leach MO, Brindle KM, Evelhoch JL, Griffiths JR, Horsman MR, Jackson A, Jayson GC, Judson IR, Knopp MV, Maxwell RJ, McIntyre D, Padhani AR, Price P, Rathbone R, Rustin GJ, Tofts PS, Tozer GM, Vennart W, Waterton JC, Williams SR, Workman P, Pharmacodynamic/Pharmacokinetic Technologies Advisory Committee DDORUK (2005) The assessment of anti-angiogenic and anti-vascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations. Br J Cancer 92(9):1599–1610
Lee V, Rusinek H, Bokacheva L, Huang A, Oesingmann N, Chen Q, Kaur M, Prince K, Song T, Kramer E, Leonard E (2007) Renal function measurements from MR renography and a simplified multicompartmental model. Am J Physiol Renal Physiol 292(5):F1548–F1559
Li X, Rooney WD, Springer CS (2005) A unified magnetic resonance imaging pharmacokinetic theory: intravascular and extracellular contrast reagents. Magn Reson Med 54(6):1351–1359. doi:10.1002/mrm.20684
Luypaert R, Sourbron S, de Mey J (2011) Validity of perfusion parameters obtained using the modified Tofts model: a simulation study. Magn Reson Med 65(5):1491–1497
Luypaert R, Ingrisch M, Sourbron S, de Mey J (2012) The Akaike information criterion in DCE-MRI: does it improve the haemodynamic parameter estimates? Phys Med Biol 57(11):3609–3628
Markwardt CB (2009) Non-linear Least-squares Fitting in IDL with MPFIT. In: Bohlender DA, Durand D, Dowler P (eds) Astronomical Society of the Pacific Conference Series, vol 411, pp 251–+, 0902.2850
Materne R, Smith AM, Peeters F, Dehoux JP, Keyeux A, Horsmans Y, Beers BEV (2002) Assessment of hepatic perfusion parameters with dynamic MRI. Magn Reson Med 47(1):135–142
Meier P, Zierler KL (1954) On the theory of the indicator-dilution method for measurement of blood flow and volume. J Appl Physiol 6(12):731–744
Michaelis LC, Ratain MJ (2006) Measuring response in a post-RECIST world: from black and white to shades of grey. Nat Rev Cancer 6(5):409–414
Michaely HJ, Kramer H, Oesingmann N, Lodemann KP, Miserock K, Reiser MF, Schoenberg SO (2007) Intraindividual comparison of MR-renal perfusion imaging at 1.5 T and 3.0 T. Invest Radiol 42(6):406–411
Miles KA, Griffiths MR, Fuentes MA (2001) Standardized perfusion value: universal CT contrast enhancement scale that correlates with FDG PET in lung nodules. Radiology 220(2):548–553
Miles KA, Lee TY, Goh V, Klotz E, Cuenod C, Bisdas S, Groves AM, Hayball MP, Alonzi R, Brunner T, Group ECMCIN (2012) Current status and guidelines for the assessment of tumour vascular support with dynamic contrast-enhanced computed tomography. Eur Radiol 22(7):1430–1441
Naish JH, Kershaw LE, Buckley DL, Jackson A, Waterton JC, Parker GJM (2009) Modeling of contrast agent kinetics in the lung using T1-weighted dynamic contrast-enhanced MRI. Magn Reson Med 61(6):1507–1514
Naish JH, McGrath DM, Bains LJ, Passera K, Roberts C, Watson Y, Cheung S, Taylor MB, Logue JP, Buckley DL, Tessier J, Young H, Waterton JC, Parker GJM (2011) Comparison of dynamic contrast-enhanced MRI and dynamic contrast-enhanced CT biomarkers in bladder cancer. Magn Reson Med 66(1):219–226
Nikolaou K, Schoenberg SO, Brix G, Goldman JP, Attenberger U, Kuehn B, Dietrich O, Reiser MF (2004) Quantification of pulmonary blood flow and volume in healthy volunteers by dynamic contrast-enhanced magnetic resonance imaging using a parallel imaging technique. Invest Radiol 39(9):537–545
Notohamiprodjo M, Reiser MF, Sourbron SP (2010) Diffusion and perfusion of the kidney. Eur J Radiol 76(3):337–347
O’Connor JPB, Jackson A, Parker GJM, Jayson GC (2007) DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents. Br J Cancer 96(2):189–195
O’Connor JPB, Jackson A, Asselin MC, Buckley DL, Parker GJM, Jayson GC (2008) Quantitative imaging biomarkers in the clinical development of targeted therapeutics: current and future perspectives. Lancet Oncol 9(8):766–776
O’Connor JPB, Carano RAD, Clamp AR, Ross J, Ho CCK, Jackson A, Parker GJM, Rose CJ, Peale FV, Friesenhahn M, Mitchell CL, Watson Y, Roberts C, Hope L, Cheung S, Reslan HB, Go MAT, Pacheco GJ, Wu X, Cao TC, Ross S, Buonaccorsi GA, Davies K, Hasan J, Thornton P, del Puerto O, Ferrara N, van Bruggen N, Jayson GC (2009) Quantifying antivascular effects of monoclonal antibodies to vascular endothelial growth factor: insights from imaging. Clin Cancer Res 15(21):6674–6682
O’Connor JPB, Jackson A, Parker GJM, Roberts C, Jayson GC (2012) Dynamic contrast-enhanced MRI in clinical trials of antivascular therapies. Nat Rev Clin Oncol 9(3):167–177
Pack NA, DiBella EVR (2010) Comparison of myocardial perfusion estimates from dynamic contrast-enhanced magnetic resonance imaging with four quantitative analysis methods. Magn Reson Med 64(1):125–137
Padhani AR, Hayes C, Landau S, Leach MO (2002) Reproducibility of quantitative dynamic MRI of normal human tissues. NMR Biomed 15(2):143–153
Parker GJM, Roberts C, Macdonald A, Buonaccorsi GA, Cheung S, Buckley DL, Jackson A, Watson Y, Davies K, Jayson GC (2006) Experimentally-derived functional form for a population-averaged high-temporal-resolution arterial input function for dynamic contrast-enhanced MRI. Magn Reson Med 56(5):993–1000. doi:10.1002/mrm.21066
Pedersen M, Shi Y, Anderson P, dkilde Jø rgensen HS, Djurhuus J, Gordon I, kiaer JF (2004) Quantitation of differential renal blood flow and renal function using dynamic contrast-enhanced MRI in rats. Magn Reson Med 51(3):510–517
Petersen ET, Zimine I, Ho YCL, Golay X (2006) Non-invasive measurement of perfusion: a critical review of arterial spin labelling techniques. Br J Radiol 79(944):688–701
Pintaske J, Martirosian P, Graf H, Erb G, Lodemann KP, Claussen CD, Schick F (2006) 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 41(3):213–221
Pradel C, Siauve N, Bruneteau G, Clement O, de Bazelaire C, Frouin F, Wedge SR, Tessier JL, Robert PH, Frija G, Cuenod CA (2003) Reduced capillary perfusion and permeability in human tumour xenografts treated with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR imaging and macromolecular contrast media. Magn Reson Imaging 21(8):845–851
Roberts HC, Roberts TPL, Lee TY, Dillon WP (2002) Dynamic, contrast-enhanced CT of human brain tumors: quantitative assessment of blood volume, blood flow, and microvascular permeability: report of two cases. AJNR Am J Neuroradiol 23(5):828–832
Roberts C, Buckley DL, Parker GJM (2006) Comparison of errors associated with single- and multi-bolus injection protocols in low-temporal-resolution dynamic contrast-enhanced tracer kinetic analysis. Magn Reson Med 56(3):611–619
Sahani DV, Kalva SP, Hamberg LM, Hahn PF, Willett CG, Saini S, Mueller PR, Lee TY (2005) Assessing tumor perfusion and treatment response in rectal cancer with multisection CT: initial observations. Radiology 234(3):785–792
Scherr MK, Seitz M, Müller-Lisse UG, Ingrisch M, Reiser MF, Müller-Lisse UL (2010) MR-perfusion (MRP) and diffusion-weighted imaging (DWI) in prostate cancer: quantitative and model-based gadobenate dimeglumine MRP parameters in detection of prostate cancer. Eur J Radiol 76(3):359–366
Schick F (2005) Whole-body MRI at high field: technical limits and clinical potential. Eur Radiol 15(5):946–959
Schoenberg S, Dietrich O, Reiser M (2007) Parallel imaging in clinical MR applications. Springer, Berlin
Sommer WH, Sourbron S, Huppertz A, Ingrisch M, Reiser MF, Zech CJ (2012) Contrast agents as a biological marker in magnetic resonance imaging of the liver: conventional and new approaches. Abdom Imaging 37(2):164–179
Song T, Laine AF, Chen Q, Rusinek H, Bokacheva L, Lim RP, Laub G, Kroeker R, Lee VS (2009) Optimal k-space sampling for dynamic contrast-enhanced MRI with an application to MR renography. Magn Reson Med 61(5):1242–1248
Sourbron S (2010) Technical aspects of MR perfusion. Eur J Radiol 76(3):304–313
Sourbron SP, Buckley DL (2011) On the scope and interpretation of the Tofts models for DCE-MRI. Magn Reson Med 66(3):735–745
Sourbron SP, Buckley DL (2012) Tracer kinetic modelling in MRI: estimating perfusion and capillary permeability. Phys Med Biol 57(2):R1–33
Sourbron S, Biffar A, Ingrisch M, Fierens Y, Luypaert R (2009) PMI0.4: platform for research in medical imaging. In: Proceedings of the ESMRMB, Antalya
Sourbron S, Dujardin M, Makkat S, Luypaert R (2007) Pixel-by-pixel deconvolution of bolus-tracking data: optimization and implementation. Phys Med Biol 52(2):429–447
Sourbron SP, Michaely HJ, Reiser MF, Schoenberg SO (2008) MRI-measurement of perfusion and glomerular filtration in the human kidney with a separable compartment model. Invest Radiol 43(1):40–48
Sourbron S, Heilmann M, Biffar A, Walczak C, Vautier J, Volk A, Peller M (2009) Bolus-tracking MRI with a simultaneous T1- and T2*-measurement. Magn Reson Med 62(3):672–681
Sourbron S, Ingrisch M, Siefert A, Reiser M, Herrmann K (2009) Quantification of cerebral blood flow, cerebral blood volume, and blood–brain-barrier leakage with DCE-MRI. Magn Reson Med 62(1):205–217
Stewart EE, Chen X, Hadway J, Lee TY (2008) Hepatic perfusion in a tumor model using DCE-CT: an accuracy and precision study. Phys Med Biol 53(16):4249–4267
Stewart EE, Sun H, Chen X, Schafer PH, Chen Y, Garcia BM, Lee TY (2012) Effect of an angiogenesis inhibitor on hepatic tumor perfusion and the implications for adjuvant cytotoxic therapy. Radiology 264(1):68–77
Tacelli N, Remy-Jardin M, Copin MC, Scherpereel A, Mensier E, Jaillard S, Lafitte JJ, Klotz E, Duhamel A, Remy J (2010) Assessment of non-small cell lung cancer perfusion: pathologic-CT correlation in 15 patients. Radiology 257(3):863–871
Tateishi U, Kusumoto M, Nishihara H, Nagashima K, Morikawa T, Moriyama N (2002) Contrast-enhanced dynamic computed tomography for the evaluation of tumor angiogenesis in patients with lung carcinoma. Cancer Biochem Biophys 95(4):835–842
Tofts PS (1997) Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging 7(1):91–101
Tofts PS, Kermode AG (1991) Measurement of the blood–brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med 17(2):357–367
Tofts PS, Brix G, Buckley DL, Evelhoch JL, Henderson E, Knopp MV, Larsson HB, Lee TY, Mayr NA, Parker GJ, Port RE, Taylor J, Weisskoff RM (1999) Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging 10(3):223–232
Türkbey B, Thomasson D, Pang Y, Bernardo M, Choyke PL (2010) The role of dynamic contrast-enhanced MRI in cancer diagnosis and treatment. Diagn Interv Radiol 16(3):186–192
Utz W, Greiser A, Niendorf T, Dietz R, Schulz-Menger J (2008) Single- or dual-bolus approach for the assessment of myocardial perfusion reserve in quantitative MR perfusion imaging. Magn Reson Med 59(6):1373–1377
Wang Y, Huang W, Panicek DM, Schwartz LH, Koutcher JA (2008) Feasibility of using limited-population-based arterial input function for pharmacokinetic modeling of osteosarcoma dynamic contrast-enhanced MRI data. Magn Reson Med 59(5):1183–1189. doi:10.1002/mrm.21432
Williams R, Hudson JM, Lloyd BA, Sureshkumar AR, Lueck G, Milot L, Atri M, Bjarnason GA, Burns PN (2011) Dynamic microbubble contrast-enhanced US to measure tumor response to targeted therapy: a proposed clinical protocol with results from renal cell carcinoma patients receiving antiangiogenic therapy. Radiology 260(2):581–590
Yankeelov TE, Luci JJ, Lepage M, Li R, Debusk L, Lin PC, Price RR, Gore JC (2005) Quantitative pharmacokinetic analysis of DCE-MRI data without an arterial input function: a reference region model. Magn Reson Imaging 23(4):519–529
Yankeelov TE, Lepage M, Chakravarthy A, Broome EE, Niermann KJ, Kelley MC, Meszoely I, Mayer IA, Herman CR, McManus K, Price RR, Gore JC (2007) Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results. Magn Reson Imaging 25(1):1–13. doi:10.1016/j.mri.2006.09.006
Zhang JL, Rusinek H, Bokacheva L, Lerman LO, Chen Q, Prince C, Oesingmann N, Song T, Lee VS (2008) Functional assessment of the kidney from magnetic resonance and computed tomography renography: impulse retention approach to a multicompartment model. Magn Reson Med 59(2):278–288
Zhu AX, Holalkere NS, Muzikansky A, Horgan K, Sahani DV (2008) Early antiangiogenic activity of bevacizumab evaluated by computed tomography perfusion scan in patients with advanced hepatocellular carcinoma. Oncologist 13(2):120–125
Zöllner FG, Weisser G, Reich M, Kaiser S, Schoenberg SO, Sourbron SP, Schad LR (2013) UMMPerfusion: an Open Source Software tool towards quantitative MRI perfusion analysis in clinical routine. J Digit Imaging 26(2):344–352
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Ingrisch, M., Sourbron, S. Tracer-kinetic modeling of dynamic contrast-enhanced MRI and CT: a primer. J Pharmacokinet Pharmacodyn 40, 281–300 (2013). https://doi.org/10.1007/s10928-013-9315-3
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DOI: https://doi.org/10.1007/s10928-013-9315-3