A Babsky, Ju Shenghong - Apparent diffusion coefficient of waterin evaluation of treatment response in animal body tumors - страница 3

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DWI is a powerful, non-invasive MRI tool that provides unique information related to structural, cellular, apoptotic, and necrotic changes in tumor tissue. The technique can be used widely for tumor detection and characterization and for monitoring of re­sponse to treatment. Effective tumor therapy is usually associated with an increase in ADC values, although exceptions may occur. WaterADC appears to have the ability to predict treatment response to chemotherapy. However, there are several challenges to wider use of DWI in cancer patients. These include a lack of accepted standards for data acquisition and analysis, variability of ADC changes depending on tumor cell type and location, motion effects on body tumorADC measurements, incomplete theoretical understanding of DWI in ECS and ICS, and poorly understood multiexponential decay components which affect the calculated ADC values. Thus, DWI protocols and analyses need to be adapted to individual tumor types, anatomic locations and therapies. We also need a better understanding of how tumor water ADC measurements can be com­bined with results of other diagnostic modalities, such as 23Na MRI, 31P MR spectro­scopy, positron emission tomography, destructive chemical analysis, and histology, to improve our assessment of prognosis and better monitoring oftherapeutic efficiency.


The authors thank Samuel G. Jennings for valuable comments and assistance in the preparation of the manuscript.


A. M. Бабський 1,2, Ш. Джи 1,3, Н. Банзал 1

1 Відділ радіологіїіндіанського університету, Індіанаполіс, Індіана 46202, США 2Львівський національний університет імені Івана Франка, вул. Грушевського, 4, Львів 79005, Україна 3Центральний госпіталь Південно-східного університету, Нанджін 210009,

Народна Республіка Китай e-mail: ababsky@iupui.edu

У статті підсумовано власні результати авторів і літературні дані, присвячені ви­користанню показників дифузії води, що вимірюються методом дифузійно-граді-

єнтних зображень ядерно-магнітного резонансу, для оцінки структурних та внутріш-ньоклітинниих змін, пов'язаних із апоптозними чи некротичними трансформаціями у ракових пухлинах. Обговорюється можливість використання змін коефіцієнта ди­фузії води для ранньої діагностики, оцінки ефективності протипухлинної терапії та з'ясування механізмів канцерогенезу на прикладах експериментальних пухлин, прищеплених тваринам.

Ключові слова: пухлина, хіміотерапія, коефіцієнт дифузії води, Натрій, ядерно-магнітний резонанс.


A. M. Бабский [2], Ш. Джи 1,3, Н. Банзал [3]

Ютдел радиологии Индианского университета, Индианаполис, Индиана 46202, США 2Львовский национальный университет имени Ивана Франко, ул. Грушевского, 4, Львов 79005, Украина 3 Центральный госпиталь Юго-восточного университета, Нанджин 210009, Народная Республика Китай

В статье подытожены результаты авторов и литературные данные посвященные использованию показателей диффузии воды, которые измеряются с использовани­ем диффузионно-градиентных изображений ядерно-магнитного резонанса, для оценки структурных и внутриклеточных изменений, связанных с апоптозными или некротическими трансформациями в раковых опухолях. Обсуждается возможность использования изменений коэффициента диффузии воды для ранней диагностики, оценки эффективности противоопухолевой терапии и выяснения механизмов канце-рогененза на примерах экспериментальных опухолей у животных.

2. Chisholm R.A., Stenning S., Hawkins T.D. The accuracy of volumetric measurement of high-grade gliomas. Clin. Radiol, 1989; 40: 17-21.

3. James K., Eisenhauer E., Christian M. et al. Measuring response in solid tumors: unidimen-sional versus bidimensional measurement. J. Natl. Cancer Inst, 1999; 91: 523-528.

4. MacDonald D.R., Cascino T.L., Schold S.C., Jr., Cairncross J.G. Response criteria for phase II studies ofsupratentorial malignantglioma. J. Clin. Oncol, 1990; 8: 1277-1280.

5. Belhocine T., Steinmetz N., Green A., Rigo P. In vivo imaging of chemotherapy-induced apop­tosis in human cancers. Ann. N. Y. Acad. Sci, 2003; 1010: 525-529.

6. Blankenberg F., Mari C., Strauss H.W. Imaging cell death in vivo. Q. J. Nucl. Med, 2003; 47:


7. Nelson S.J., Cha S. Imaging glioblastoma multiforme. Cancer J, 2003; 9: 134-145.

8. Ross B.D., Chenevert T.L., Garwood M. et al. Evaluation of (E)-2'-deoxy-2'-(fluoromethylene) cytidine on the 9L rat brain tumor model using MRI. NMR Biomed, 2003; 16: 67-76.

9. Spence A.M., Mankoff D.A., Muzi M. Positron emission tomography imaging of brain tumors. Neuroimaging Clin. N. Am, 2003; 13: 717-739.

10. Van de Wiele C,. Lahorte C., Oyen W. et al. Nuclear medicine imaging to predict response to radiotherapy: a review. Int. J. Radiat. Oncol. Biol. Phys, 2003; 55: 5-15.

11. Ross B., Chenvert T., Kim B., Ben-Yoseph O. Magnetic resonanse imaging and spectroscopy: application to experimental neurooncology. Quart. Magn. Resn. Biol. Med, 1994; 1: 89-106.

13. Geschwind J.F., Artemov D., Abraham S. et al. Chemoembolization of liver tumor in a rabbit model: assessment of tumor cell death with diffusion-weighted MR imaging and histologic analysis. J. Vasc. Interv. Radiol, 2000;11: 1245-1255.

14. Stegman L.D., Rehemtulla A., Hamstra D.A. et al. Diffusion MRI detects early events in the response of a glioma model to the yeast cytosine deaminase gene therapy strategy. Gene. Ther, 2000; 7: 1005-1010.

15. Chenevert T.L., Stegman L.D., Taylor J.M. et al. Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors. J. Natl. Cancer Inst, 2000; 92:


16. DeVries A.F., Kremser C., Hein P.A. et al. Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma. Int. J. Radiat. Oncol. Biol. Phys, 2003; 56: 958-965.

17. Dzik-Jurasz A., Domenig C., George M. et al. Diffusion MRI for prediction of response of rectal cancer to chemoradiation. Lancet, 2002; 360: 307-308.

18. Galons J.P., Altbach M.I., Paine-Murrieta G.D. et al. Early increases in breast tumor xenograft water mobility in response to paclitaxel therapy detected by non-invasive diffusion magnetic resonance imaging. Neoplasia, 1999; 1: 113-117.

19. Thoeny H.C., De Keyzer F., Chen F. et al. Diffusion-weighted MR imaging in monitoring the effect of a vascular targeting agent on rhabdomyosarcoma in rats. Radiology, 2005; 234:


20. Chenevert T.L., McKeever P.E., Ross B.D. Monitoring early response of experimental brain tumors to therapy using diffusion magnetic resonance imaging. Clin. Cancer Res, 1997; 3:


21. Chinnaiyan A.M., Prasad U., Shankar S. et al. Combined effect of tumor necrosis factor-relat­ed apoptosis-inducing ligand and ionizing radiation in breast cancer therapy. Proc. Natl. Acad. Sci. USA, 2000; 97: 1754-1759.

22. Hakumaki J.M., Poptani H., Puumalainen A.M. et al. Quantitative 1H nuclear magnetic reso­nance diffusion spectroscopy of BT4C rat glioma during thymidine kinase-mediated gene therapy in vivo: identification ofapoptotic response. Cancer Res, 1998; 58: 3791-3799.

23. Poptani H., Puumalainen A.M., Grohn O.H. et al. Monitoring thymidine kinase and ganciclo-vir-induced changes in rat malignant glioma in vivo by nuclear magnetic resonance imaging. Cancer Gene. Ther, 1998; 5: 101-109.

24. Zhao M., Pipe J.G., Bonnett J., Evelhoch J.L. Early detection of treatment response by diffusion-weighted 1H-NMRspectroscopy in a murine tumour in vivo. Br. J. Cancer, 1996; 73: 61-64.

25. Hein P.A., Kremser C., Judmaier W. et al. Diffusion-weighted magnetic resonance imaging for monitoring diffusion changes in rectal carcinoma during combined, preoperative chemoradia­tion: preliminary results ofa prospective study. Eur. J. Radiol, 2003; 45: 214-222.

26. Kremser C., Judmaier W., Hein P. et al. Preliminary results on the influence of chemoradiation on apparent diffusion coefficients of primary rectal carcinoma measured by magnetic reso­nance imaging. Strahlenther. Onkol, 2003; 179: 641-649.

27. Mardor Y., Pfeffer R., Spiegelmann R. et al. Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging. J. Clin. Oncol, 2003; 21: 1094-1100.

28. Ross B.D., Moffat B.A., Lawrence T.S. et al. Evaluation of cancer therapy using diffusion magnetic resonance imaging. Mol. Cancer Ther, 2003; 2: 581-587.

29. Koh D.M., Collins D.J. Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am. J. Roentgenol, 2007; 188: 1622-1635.

30. Sykova E., Svoboda J., Polak J., Chvatal A. Extracellular volume fraction and diffusion cha­racteristics during progressive ischemia and terminal anoxia in the spinal cord of the rat. J. Cereb. Blood. Flow. Metab, 1994; 14: 301-311.

31. Sugahara T., Korogi Y., Kochi M. et al. Usefulness of diffusion-weighted MRI with echo-planar technique in the evaluation of cellularity in gliomas. J. Magn. Reson. Imaging, 1999; 9: 53-60.

32. Lyng H., Haraldseth O., Rofstad E.K. Measurement of cell density and necrotic fraction in human melanoma xenografts by diffusion weighted magnetic resonance imaging. Magn. Re-son. Med, 2000; 43: 828-836.

33. Guo A.C., Cummings T.J., Dash R.C., Provenzale J.M. Lymphomas and high-grade astrocy­tomas: comparison of water diffusibility and histologic characteristics. Radiology, 2002; 224:


34. Szafer A., Zhong J., Gore J.C. Theoretical model for water diffusion in tissues. Magn. Reson. Med, 1995; 33: 697-712.

35. Moffat B.A., Chenevert T.L., Lawrence T.S. et al. Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response. Proc. Natl. Acad. Sci. USA, 2005; 102: 5524-5529.

36. Babsky A.M., Topper S., Zhang H. et al. Evaluation of extra- and intracellular apparent diffu­sion coefficient of sodium in rat skeletal muscle: effects of prolonged ischemia. Magn. Re­son. Med, 2008; 59: 485-491.

37. Duong T.Q., Ackerman J.J., Ying H.S., Neil J.J. Evaluation of extra- and intracellular apparent diffusion in normal and globally ischemic rat brain via 19F NMR. Magn. Reson. Med, 1998; 40: 1-13.

38. Schepkin V., Chenevert T., Kuszpit K. et al. Sodium and proton diffusion MRI as biomarkers for early therapeutic response in subcutaneous tumors. Magn. Reson. Imaging, 2006; 24:


39. Schepkin V.D., Lee K.C., Kuszpit K. et al. Proton and sodium MRI assessment of emerging tumorchemotherapeuticresistance. NMR Biomed, 2006; 19: 1035-1042.

40. Babsky A., Hekmatyar S., Zhang H. et al. Application of 23Na MRI to monitor chemotherapeu-tic response in RIF-1 tumors. Neoplasia, 2005; 7: 658-666.

41. Babsky A., Hekmatyar S., Zhang H. et al. Predicting and monitoring response to chemo­therapy by 1,3-bis(2-chloroethyl)-1-nitrosourea in subcutaneously implanted 9L glioma using the apparent diffusion coefficient of water and 23Na MRI. J. Magn. Reson. Imaging, 2006; 24: 132-139.

42. Babsky A.M., Zhang H., Hekmatyar S.K. et al. Monitoring chemotherapeutic response in RIF-1 tumors by single-quantum and triple-quantum-filtered 23Na MRI, 1H diffusion-weighted MRI and PET imaging. Magn. Reson. Imaging, 2007; 25: 1015-1023.

43. Thoeny H.C., De Keyzer F., Chen F. et al. Diffusion-weighted magnetic resonance imaging allows noninvasive in vivo monitoring of the effects of combretastatin a-4 phosphate after repeated administration. Neoplasia, 2005; 7: 779-787.

44. Lemaire L., Howe F.A., Rodrigues L.M., Griffiths J.R. Assessment of induced rat mammary tumour response to chemotherapy using the apparent diffusion coefficient oftissue water as determined by diffusion-weighted 1H-NMR spectroscopy in vivo. MAGMA, 1999; 8: 20-26.

45. Zhao M., Pipe J.G., Bonnett J., Evelhoch J.L. Early detection of treatment response by diffu­sion-weighted 1H-NMR spectroscopy in a murine tumour in vivo. Br. J. Cancer, 1996; 73:


46. Seierstad T., Folkvord S., Roe K. et al. Early changes in apparent diffusion coefficient predict the quantitative antitumoral activity of capecitabine, oxaliplatin, and irradiation in HT29 xeno­grafts in athymic nude mice. Neoplasia, 2007; 9: 392-400.

47. Galons J.P., Altbach M.I., Paine-Murrieta G.D. et al. Early increases in breast tumor xenograft water mobility in response to paclitaxel therapy detected by non-invasive diffusion magnetic resonance imaging. Neoplasia, 1999; 1: 113-117.

48. Morse D.L., Galons J.P., Payne C.M. et al. MRI-measured water mobility increases in response to chemotherapy via multiple cell-death mechanisms. NMR Biomed, 2007; 20: 602-614.

49. Thoeny H.C., De Keyzer F., Vandecaveye V. et al. Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging. Radiolo­gy, 2005; 237: 492-499.

50. Seierstad T., Roe K., Olsen D.R. Noninvasive monitoring of radiation-induced treatment re­sponse using proton magnetic resonance spectroscopy and diffusion-weighted magnetic resonance imaging in a colorectal tumor model. Radiother. Oncol, 2007; 85: 187-194.

51. Roth Y., Tichler T., Kostenich G. et al. High-b-value diffusion-weighted MR imaging for pre­treatment prediction and early monitoring of tumor response to therapy in mice. Radiology, 2004; 232: 685-692.

52. Schepkin V.D., Ross B.D., Chenevert T.L. et al. Sodium magnetic resonance imaging of che-motherapeutic response in a rat glioma. Magn. Reson. Med, 2005; 53: 85-92.

53. Jordan B.F., Runquist M., Raghunand N. et al. Dynamic contrast-enhanced and diffusion MRI show rapid and dramatic changes in tumor microenvironment in response to inhibition of HIF-1alpha using PX-478. Neoplasia, 2005; 7: 475-4854.

54 Le Bihan D., Delannoy J., Levin R.L. Temperature mapping with MR imaging of molecular diffusion: application to hyperthermia. Radiology, 1989; 171: 853-857.

55. Morvan D., Leroy-Willig A. Simultaneous measurements of diffusion and transverse rela­xation in exercising skeletal muscle. Magn. Reson. Imaging, 1995; 13: 943-948.

56. Braunschweiger P.G. Effect of cyclophosphamide on the pathophysiology of RIF-1 solid tu­mors. Cancer Res, 1988; 48: 4206-4210.

57. Padhani A., Liu G., Koh D.M. et al. Diffusion weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations. Neoplasia, 2009; 11: 102-125.

58. Boucher E., Corbinais S., Brissot P. et al. Treatment of hepatocellular carcinoma (HCC) with systemic chemotherapy combining epirubicin, cisplatinum and infusional 5-fluorouracil (ECF regimen). Cancer Chemother. Pharmacol, 2002; 50: 305-308.

59. Iwamiya T., Sawada S., Ohta Y. Repeated arterial infusion chemotherapy for inoperable he­patocellular carcinoma using an implantable drug delivery system. Cancer Chemother. Pharmacol, 1994; 33 Suppl: S134-138.

60. Yanase K., Yoshiji H., Ikenaka Y. et al. Synergistic inhibition of hepatocellular carcinoma growth and hepatocarcinogenesis by combination of 5-fluorouracil and angiotensin-conver-ting enzyme inhibitorvia anti-angiogenic activities. Oncol. Rep, 2007; 17: 441-446.

61. Helmer K.G., Meiler M.R., Sotak C.H., Petruccelli J.D. Comparison ofthe return-to-the-origin probability and the apparent diffusion coefficient of water as indicators of necrosis in RIF-1 tumors. Magn. Reson. Med, 2003; 49: 468-478.

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A Babsky, Ju Shenghong - Apparent diffusion coefficient of waterin evaluation of treatment response in animal body tumors