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Brain metastatic volume and white matter lesions in advanced cancer patients

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Abstract

Brain white matter T2 hyperintensities (WMH) are a frequent MRI finding in adults, both in asymptomatic and in cancer patients. The aim of our study is to determine the relationship between quantitative measures of the volume of WMH and the volume of brain metastatic lesions at the first MRI diagnosis of brain metastases in a population of advanced cancer patients. Brain MRI examinations of 162 consecutive patients were included and 984 brain metastases at first diagnosis were studied. Axial FLAIR images were used to visualize peri-lesional edema and to segment WMH; multiplanar contrast-enhanced T1-weighted TSE images were used to detect, count, segment and measure metastatic lesions. Segmentation of WMH on FLAIR images was performed after linear image registration to eliminate peri-lesional edema from the WMH masks. The distribution of the volumes of metastatic lesions was significantly different (ANOVA, p = 0.003) among all patients and among lung cancer patients (ANOVA, p = 0.003), with higher volumes of metastatic lesions in a higher proportion of patients when WMH were absent. There were no significant differences among groups at the 10 cc threshold of WMH. We found that volumes of brain metastases at the first MR diagnosis in a sample of advanced cancer patients and in the group of lung cancer patients were significantly lower if WMH were present; we suggest that WMH may represent a clinical MRI bio-marker of brain micro-environment resistance to the occurrence of brain metastases.

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References

  1. Peretti-Viton P, Margain D, Murayama N et al (1991) Brain metastases. J Neuroradiol 18:161–172

    PubMed  CAS  Google Scholar 

  2. Suh JH (2010) Stereotactic radiosurgery for the management of brain metastases. N Engl J Med 362(12):1119–1127

    Article  PubMed  CAS  Google Scholar 

  3. Jernal A, Murray T, Samuels A et al (2003) Cancer statistics. CA Cancer J Clin 53:5–26

    Article  Google Scholar 

  4. Nagao E, Yoshiura T, Hiwatashi A et al (2011) 3D turbo spin-echo sequence with motion-sensitized driven-equilibrium preparation for detection of brain metastases on 3T MR imaging. AJNR Am J Neuroradiol 32:664–670

    Article  PubMed  CAS  Google Scholar 

  5. Qian Y-F, Yu C-L, Zhang C et al (2008) MR T1-weighted inversion recovery imaging in detecting brain metastases: could it replace T1-weighted spin-echo imaging? AJNR Am J Neuroradiol 29:701–704

    Article  PubMed  Google Scholar 

  6. Luzzi KJ, MacDonald IC, Schmidt EE, Kerkvliet N, Morris VL, Chambers AF, Groom AC (1998) Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol 153(3):865–873

    Article  PubMed  CAS  Google Scholar 

  7. Wirtz D, Konstantopoulos K, Searson PC (2011) The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer 11(7):512–522

    Article  PubMed  CAS  Google Scholar 

  8. Weiss L (2000) Metastasis of cancer: a conceptual history from antiquity to the 1990s. Cancer Metastasis Rev 19(3–4):193–383

    Article  Google Scholar 

  9. Fidler IJ, Yano S, Zhang RD et al (2002) The seed and soil hypothesis: vascularization and brain metastases. Lancet Oncol 3(1):53–57

    Article  PubMed  CAS  Google Scholar 

  10. Paget S (1989) The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev 8:98–101

    PubMed  CAS  Google Scholar 

  11. Sleeman JP (2012) The metastatic niche and stromal progression. Cancer Metastasis Rev 31(3–4):429–440

    Article  PubMed  CAS  Google Scholar 

  12. Psaila B, Kaplan RN, Port ER, Lyden D (2006–2007) Priming the ‘soil’ for breast cancer metastasis: the pre-metastatic niche. Breast Dis 26:65–74

    Google Scholar 

  13. Sleeman JP, Nazarenko I, Thiele W (2011) Do all roads lead to Rome? Routes to metastasis development. Int J Cancer 128(11):2511–2526

    Article  PubMed  CAS  Google Scholar 

  14. Carlini MJ, De Lorenzo MS, Puricelli L (2011) Cross-talk between tumor cells and the microenvironment at the metastatic niche. Curr Pharm Biotechnol 12(11):1900–1908

    Article  PubMed  CAS  Google Scholar 

  15. Luissint AC, Artus C, Glacial F, Ganeshamoorthy K, Couraud PO (2012) Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation. Fluids Barriers CNS 9(1):23

    Article  PubMed  Google Scholar 

  16. Al Ahmad A, Gassmann M, Ogunshola OO (2009) Maintaining blood-brain barrier integrity: pericytes perform better than astrocytes during prolonged oxygen deprivation. J Cell Physiol 218(3):612–622

    Article  PubMed  CAS  Google Scholar 

  17. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD (2006) Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 1(3):223–236

    Article  PubMed  Google Scholar 

  18. Carbonell WS, Ansorge O, Sibson N, Muschel R (2009) The vascular basement membrane as “soil” in brain metastasis. PLoS ONE 4(6):e5857

    Article  PubMed  Google Scholar 

  19. Vernooij MW, Ikram MA, Tanghe HL, Vincent AJ, Hofman A, Krestin GP, Niessen WJ, Breteler MM, van der Lugt A (2007) Incidental findings on brain MRI in the general population. N Engl J Med 357(18):1821–1828

    Article  PubMed  CAS  Google Scholar 

  20. Mazzone PJ, Marchi N, Fazio V, Taylor JM, Masaryk T, Bury L, Mekhail T, Janigro D (2009) Small vessel ischemic disease of the brain and brain metastases in lung cancer patients. PLoS ONE 4(9):e7242

    Article  PubMed  Google Scholar 

  21. Brown WR, Thore CR (2011) Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol 37(1):56–74

    Article  PubMed  CAS  Google Scholar 

  22. Brown WR, Moody DM, Thore CR, Anstrom JA, Challa VR (2009) Microvascular changes in the white mater in dementia. J Neurol Sci 283(1–2):28–31

    Article  PubMed  Google Scholar 

  23. Gouw AA, van der Flier WM, Pantoni L, Inzitari D, Erkinjuntti T, Wahlund LO, Waldemar G, Schmidt R, Fazekas F, Scheltens P, Barkhof F, LADIS study group (2008) On the etiology of incident brain lacunes: longitudinal observations from the LADIS study. Stroke 39(11):3083–3085

    Article  PubMed  Google Scholar 

  24. Spolveri S, Baruffi MC, Cappelletti C, Semerano F, Rossi S, Pracucci G, Inzitari D (1998) Vascular risk factors linked to multiple lacunar infarcts. Cerebrovasc Dis 8(3):152–157

    Article  PubMed  CAS  Google Scholar 

  25. Pantoni L, Garcia JH (1997) Pathogenesis of leukoaraiosis: a review. Stroke 8(3):652–659

    Article  Google Scholar 

  26. O’Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB, Rockwood K, Burns A, Gauthier S, DeKosky ST (2003) Vascular cognitive impairment. Lancet Neurol 2(2):89–98

    Article  PubMed  Google Scholar 

  27. Mazziotta JC, Toga AW, Evans A et al (1995) A probabilistic atlas of the human brain: theory and rationale for its development. The International Consortium for Brain Mapping (ICBM). Neuroimage 2(2):89–101

    Article  PubMed  CAS  Google Scholar 

  28. Hanbali A, Al-Khasawneh K, Cole-Johnson C, Divine G, Ali H (2007) Protective effect of diabetes against metastasis in patients with non-small cell lung cancer. Arch Intern Med 167(5):513

    PubMed  Google Scholar 

  29. Murray ME, Vemuri P, Preboske GM, Murphy MC, Schweitzer KJ, Parisi JE, Jack CR Jr, Dickson DW (2012) A quantitative postmortem MRI design sensitive to white matter hyperintensity differences and their relationship with underlying pathology. J Neuropathol Exp Neurol. [Epub ahead of print]

  30. Fazekas F, Schmidt R, Kleinert R, Kapeller P, Roob G, Flooh E (1998) The spectrum of age-associated brain abnormalities: their measurement and histopathological correlates. J Neural Transm Suppl 53:31–39

    Article  PubMed  CAS  Google Scholar 

  31. Gouw AA, Seewann A, van der Flier WM, Barkhof F, Rozemuller AM, Scheltens P, Geurts JJ (2011) Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry 82(2):126–135

    Article  PubMed  Google Scholar 

  32. Moody DM, Thore CR, Anstrom JA, Challa VR, Langefeld CD, Brown WR (2004) Quantification of afferent vessels shows reduced brain vascular density in subjects with leukoaraiosis. Radiology 233(3):883–890

    Article  PubMed  Google Scholar 

  33. Marstrand JR, Garde E, Rostrup E, Ring P, Rosenbaum S, Mortensen EL, Larsson HB (2002) Cerebral perfusion and cerebrovascular reactivity are reduced in white matter hyperintensities. Stroke 33(4):972–976

    Article  PubMed  CAS  Google Scholar 

  34. Fukumura D, Duda DG, Munn LL, Jain RK (2010) Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical models. Microcirculation 17(3):206–225

    Article  PubMed  CAS  Google Scholar 

  35. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8:752–758

    Article  PubMed  CAS  Google Scholar 

  36. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318

    Article  PubMed  CAS  Google Scholar 

  37. Lorger M, Felding-Habermann B (2010) Capturing changes in the brain microenvironment during initial steps of breast cancer brain metastasis. Am J Pathol 176(6):2958–2971

    Article  PubMed  Google Scholar 

  38. Ropele S, Seewann A, Gouw AA, van der Flier WM, Schmidt R, Pantoni L, Inzitari D, Erkinjuntti T, Scheltens P, Wahlund LO, Waldemar G, Chabriat H, Ferro J, Hennerici M, O’Brien J, Wallin A, Langhorne P, Visser MC, Barkhof F, Fazekas F, LADIS study group (2009) Quantitation of brain tissue changes associated with white matter hyperintensities by diffusion-weighted and magnetization transfer imaging: the LADIS (Leukoaraiosis and Disability in the Elderly) study. J Magn Reson Imaging 29(2):268–274

    Article  PubMed  Google Scholar 

  39. Maillard P, Carmichael O, Harvey D, Fletcher E, Reed B, Mungas D, Decarli C (2012) FLAIR and diffusion MRI signals are independent predictors of white matter hyperintensities. AJNR Am J Neuroradiol. [Epub ahead of print]

  40. Maillard P, Fletcher E, Harvey D, Carmichael O, Reed B, Mungas D, DeCarli C (2011) White matter hyperintensity penumbra. Stroke 42(7):1917–1922

    Article  PubMed  Google Scholar 

  41. Bender ET, Tomé WA (2011) Distribution of brain metastases: implications for non-uniform dose prescriptions. Br J Radiol 84(1003):649–658

    Article  PubMed  CAS  Google Scholar 

  42. Quattrocchi CC, Errante Y, Gaudino C, Mallio CA, Giona A, Santini D, Tonini G, Zobel BB (2012) Spatial brain distribution of intra-axial metastatic lesions in breast and lung cancer patients. J Neurooncol 110(1):79–87

    Article  PubMed  CAS  Google Scholar 

  43. Graf AH, Buchberger W, Langmayr H et al (1988) Site preference of metastatic tumors of the brain. Virchows Arch A Pathol Anat Histopathol 412(5):493–498

    Article  PubMed  CAS  Google Scholar 

  44. Tsukada Y, Fouad A, Pickren JW et al (1983) Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer 52:2349–2354

    Article  PubMed  CAS  Google Scholar 

  45. Trepel M, Arap W, Pasqualini R (2002) In vivo phage display and vascular heterogeneity: implications for targeted medicine. Curr Opin Chem Biol 6:399–404

    Article  PubMed  CAS  Google Scholar 

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Diagnostic Imaging, CIR—Center for Integrated Research in Biomedicine and Bioengineering, University Campus Bio-Medico di Roma, via Alvaro del Portillo, 21, 00128, Rome, Italy

    Carlo Cosimo Quattrocchi, Yuri Errante, Carlo Augusto Mallio & Bruno Beomonte Zobel

  2. Oncology, CIR—Center for Integrated Research in Biomedicine and Bioengineering, University Campus Bio-Medico di Roma, via Alvaro del Portillo, 21, 00128, Rome, Italy

    Daniele Santini & Giuseppe Tonini

  3. Unit of Radiology, Fondazione San Raffaele, via G. Di Biasio, 1, 03043, Cassino, FR, Italy

    Carlo Cosimo Quattrocchi & Bruno Beomonte Zobel

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  1. Carlo Cosimo Quattrocchi
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  2. Yuri Errante
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Correspondence to Carlo Cosimo Quattrocchi.

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Quattrocchi, C.C., Errante, Y., Mallio, C.A. et al. Brain metastatic volume and white matter lesions in advanced cancer patients. J Neurooncol 113, 451–458 (2013). https://doi.org/10.1007/s11060-013-1137-z

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  • DOI: https://doi.org/10.1007/s11060-013-1137-z

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