Abstract
Tumour blood flow plays a key role in tumour growth, formation of metastasis, and detection and treatment of malignant tumours. Recent investigations provided increasing evidence that quantitative analysis of tumour blood flow is an indispensable prerequisite for developing novel treatment strategies and individualizing cancer therapy. Currently, however, methods for noninvasive, quantitative and high spatial resolution imaging of tumour blood flow are rare. We apply here a novel approach combining a recently established ultrafast MRI technique, that is T1-relaxation time mapping, with a tracer kinetic model. For validation of this approach, we compared the results obtained in vivo with data provided by iodoantipyrine autoradiography as a reference technique for the measurement of tumour blood flow at a high resolution in an experimental tumour model. The MRI protocol allowed quantitative mapping of tumour blood flow at spatial resolution of 250 × 250 μm2. Correlation of data from the MRI method with the iodantipyrine autoradiography revealed Spearman's correlation coefficients of Rs = 0.851 (r = 0.775, P < 0.0001) and Rs = 0.821 (r = 0.72, P = 0.014) for local and global tumour blood flow, respectively. The presented approach enables noninvasive, repeated and quantitative assessment of microvascular perfusion at high spatial resolution encompassing the entire tumour. Knowledge about the specific vascular microenvironment of tumours will form the basis for selective antivascular cancer treatment in the future. © 2001 Cancer Research Campaign http://www.bjcancer.com
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References
Bland JM and Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1: 307–310
Brix G, Semmler W, Port R, Schad LR, Layer G and Lorenz WJ (1991) Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging. J Comput Assist Tomogr 15: 621–628
Brix G, Bahner ML, Hoffmann U, Horvath A and Schreiber W (1999) Regional blood flow, capillary permeability, and compartment volumes. Measurement with dynamic CT-initial experience. Radiology 210: 269–276
Burstein D, Taratuta E and Manning WJ (1991) Factors in myocardial perfusion imaging with ultrafast MRI and Gd-DTPA administration. Magn Reson Med 20: 299–305
Daldrup HE, Shames DM, Husseini W, Wendland MF, Okuhata Y and Brasch RC (1998) Quantification of the extraction fraction for gadopentetate across breast cancer capillaries. Magn Reson Med 40: 537–543
Deichmann R and Haase A (1992) Quantification of T1 Values by SNAPSHOT-FLASH NMR Imaging. J Magn Reson 96: 608–612
Degani H, Gusis V, Weinstein D, Fields S and Strano S (1997) Mapping pathophysiological features of breast tumors by MRI at high spatial resolution. Nat Med 3: 780–782
de Vries A, Griebel J, Kremser C, Judmaier W, Gneiting T, Debbage P, Kremser T, Pfeiffer KP, Buchberger W and Lukas P (2000) Monitoring of tumor microcirculation during fractionated radiation therapy in patients with rectal carcinoma: preliminary results and implication for therapy. Radiology 217: 385–391
de Vries AF, Griebel J, Kremser C, Judmaier W, Gneiting T, Kreczy A, Ofner D, Pfeiffer KP, Brix G and Lukas P (2001) Tumor microcirculation evaluated by dynamic magnetic resonance imaging predicts therapy outcome for primary rectal carcinoma. Cancer Res 61: 2513–2516
Diesbourg LD, Prato FS, Wisenberg G, Drost DJ, Marshall TP, Carroll SE and O’Neill B (1992) Quantification of myocardial blood flow and extracellular volumes using a bolus injection of Gd-DTPA: kinetic modeling in canine ischemic disease. Magn Reson Med 23: 239–253
Donahue KM, Burstein D, Manning WJ and Gray ML (1994) Studies of Gd-DTPA relaxivity and proton exchange rates in tissue. Magn Reson Med 32: 66–76
Fritz-Hansen T, Rostrup E, Larsson HB, Sondergaard L, Ring P and Henriksen O (1996) Measurements of the arterial concentration od Gd-DTPA using MRI: a step toward quantitative perfusion imaging. Magn Reson Med 36: 225–231
Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1: 27–31
Fortner JG, Mahy AG and Schrodt GR (1961) Transplantable tumors of the Syrian (Golden) hamster. Part I: tumors of the alimentary tract, endocrine glands and melanomas. Cancer Res 21: 161–198
Griebel J, Mayr NA, de Vries A, Knopp MV, Gneiting T, Kremser C, Essig M, Hawighorst H, Lukas PH and Yuh WT (1997) Assessment of tumor microcirculation: a new role of dynamic contrast MR imaging. J Magn Reson Imaging 7: 111–119
Griebel J, Pahernik SA, Lucht R, De Vries A, Englmeier KH, Dellian M and Brix G (2001) Perfusion and permeability: can both parameters be evaluated separately from dynamic MR data. Proc Int Soc Mag Reson Med 9: 629
Goetz A (1987) Quantitative Analyse der Tumormikrozirkulation im amelanotischen Hamstermelanom A-MEL-3. Medical thesis at the university of Munich,
Hawighorst H, Weikel W, Knapstein PG, Knopp MV, Zuna I, Schoenberg SO, Vaupel P and von Kaick G (1998) Angiogenic activity of cervical carcinoma: Assessment by functional Magnetic Resonance Imaging-based parameters and a histomorphological approach in correlation with disease outcome. Clin Cancer Res 4: 2305–2311
Henderson E, Sykes J, Drost D, Weinmann HJ, Rutt BK and Lee TY (2000) Simultaneous measurement of blood flow, blood volume, and capillary permeability in mammary tumors using two different contrast agents. J Magn Reson Imaging 12: 991–1003
Hoeckel M, Schlenger K, Aral B, Mitze M, Schaffer U and Vaupel P (1996) Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56: 4509–4515
Jain RK (1998) The next frontier of molecular medicine: delivery of therapeutics. Nat Med 4: 655–657
Judd RM, Atalay MK, Rottmann GA and Zerhouni EA (1995) Effects of myocardial water exchange on T1 enhancement during bolus administration of MR contrast agents. Magn Reson Med 33: 215–223
Kety SS (1960) Measurement of local blood flow by the exchange of an inert, diffusible substance. Methods Med Res 8: 228–236
Kuhnle GE, Dellian M, Walenta S, Mueller-Klieser W and Goetz AE (1992) Simultaneous high-resolution measurement of adenosine triphosphate levels and blood flow in the hamster amelanotic melanoma A-Mel-3. J Natl Cancer Inst 84: 1642–1647
Larsson HBW, Stubgaard M, Frederiksen L, Jensen M, Henriksen O and Paulson OB (1990) Quantitation of blood-brain barrier defect by magnetic resonance imaging and Gadolinium-DTPA in patients with multiple sklerosis and brain tumors. Magn Reson Med 16: 117–131
Larsson HB, Stubgaard M, Sondergaard L and Henriksen O (1994) In vivo quantification of the unidirectional influx constant for Gd-DTPA diffusion across the myocardial capillaries with MR imaging. J Magn Reson Imaging 4: 433–440
Lyng H, Dahle GO, Kaalhus O, Skretting A and Rofstad EK (1998) Measurement of perfusion rate in human melanoma xenograts by contrast-enhanced magnetic resonance imaging. Magn Reson Med 40: 89–98
Mayr NA, Yuh WT, Magnotta VA, Ehrhardt JC, Wheeler JA, Sorosky JI, Davis CS, Wen BC, Martin DD, Pelsang RE, Buller RE, Oberley LW, Mellenberg DE and Hussey DH (1996) Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay. Int J Radiat Oncol Biol Phys 36: 623–633
Meier P and Zierler K (1963) On the theory of the indicator-dilution method for measurement of blood flow and volume. J Appl Physiol 6: 731–744
Morales MF and Smith RE (1948) On the theory of blood-tissue exchange of inert gases. VI. Validity of approximate uptake expressions. Bull Math Biophys 10: 191–200
Nekolla S, Gneiting T, Syha J, Deichmann R and Haase A (1992) T1 maps by K-space reduced snapshot-FLASH MRI. J Comput Assist Tomogr 16: 327–332
Rempp KA, Brix G, Wenz F, Becker CR, Guckel F and Lorenz WJ (1994) Quantification of regional cerebral blood flow and volume with dynamic susceptibility contrast-enhanced MR imaging. Radiology 193: 637–641
Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL and Sokoloff L (1978) Measurement of local cerebral blood flow with iodo [14C] antipyrine. Am J Physiol 234: H59–H66
Schmiedl UP, Kenney J and Maravilla KR (1991) Kinetics of pathological blood-brain-barrier permeability in an astrocytic glioma using contrast-enhanced MR. Am J Neuro Radiol 13: 5–14
Strich G, Hagan PL, Gerber KH and Slutsky RA (1985) Tissue distribution and magnetic resonance spin lattice relaxation effects of Gadolinium-DTPA. Radiology 154: 723–726
Taylor JS, Tofts PS, Port R, Evelhoch JL, Knopp M, Reddick WE, Runge VM and Mayr N (1999) MR imaging of tumor microcirculation: promise for the new millenium. J Magn Reson Imaging 10: 903–907
Tofts PS and Kermode G (1991) Measurement of the blood-brain barrier permaebility and leackage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med 17: 357–367
Tong CY, Prato FS, Wisenberg G, Lee TY, Carroll E, Sandler D, Wills J and Drost D (1993) Measurement of the extraction efficiency and distribution volume for Gd-DTPA in normal and diseased canine myocardium. Magn Reson Med 30: 337–346
Vaupel P, Kallinowski F and Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49: 6449–6465
Weidner N, Semple JP, Welch WR and Folkman J (1991) Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med 324: 1–8
Workman P, Twentyman P, Balmain A, Chaplin D, Double J, Embleton J, Newell D, Raymond R, Stables J, Stephens T and Wallace J (1998) United Kingdom co-ordinating committee on cancer research (UKCCCR) guidelines for the welfare of animals in experimental neoplasia (second edition). Br J Cancer 77: 1–10
Zierler KL (1963) Theory of use of indicators to measure blood flow and extracellular volume and calculation of transcapillary movement of tracers. Circ Res 12: 464–471
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Pahernik, S., Griebel, J., Botzlar, A. et al. Quantitative imaging of tumour blood flow by contrast-enhanced magnetic resonance imaging. Br J Cancer 85, 1655–1663 (2001). https://doi.org/10.1054/bjoc.2001.2157
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DOI: https://doi.org/10.1054/bjoc.2001.2157
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