Journal of Neuro-Oncology

, Volume 110, Issue 1, pp 79–87 | Cite as

Spatial brain distribution of intra-axial metastatic lesions in breast and lung cancer patients

  • Carlo Cosimo QuattrocchiEmail author
  • Yuri Errante
  • Chiara Gaudino
  • Carlo Augusto Mallio
  • Alessandro Giona
  • Daniele Santini
  • Giuseppe Tonini
  • Bruno Beomonte Zobel
Clinical Study


The frequency of the diagnosis of brain metastases has increased in recent years, probably due to an increased diagnostic sensitivity. Site predilection of brain lesions in oncological patients at the time of onset, may suggest mechanisms of brain-specific vulnerability to metastasis. The aim of the study is to determine the spatial distribution of intra-axial brain metastases by using voxel-wise statistics in breast and lung cancer patients. For this retrospective cross-sectional study, clinical data and MR imaging of 864 metastases at first diagnosis in 114 consecutive advanced cancer patients from 2006 to 2011 were included. Axial post-gadolinium T1 weighted images were registered to a standard template. Binary lesion masks were created after segmentation of volumes of interest. The voxel-based lesion-symptom mapping approach was used to calculate a t statistic describing the differences between groups. It was found that the lesions were more likely to be located in the parieto-occipital lobes and cerebellum for the total cohort and for the non small cell lung cancer group, and in the cerebellum for the breast cancer group. The voxel-wise inter-group comparisons showed the largest significant clusters in the cerebellum for the breast cancer group (p < 0.0008) and in the occipital lobe (p = 0.02) and cerebellum (p = 0.02) for the non small cell lung cancer group. We conclude a non-uniform distribution of metastatic brain lesions in breast and lung cancer patients that suggest differential vulnerability to metastasis in the different regions of the brain.


Brain metastasis Voxel-wise statistics Lung cancer Breast cancer 


Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11060_2012_937_MOESM1_ESM.doc (53 kb)
Supplementary material 1 (DOC 53 kb)


  1. 1.
    Peretti-Viton P, Margain D, Murayama N et al (1991) Brain metastases. J Neuroradiol 18:161–172PubMedGoogle Scholar
  2. 2.
    Suh JH (2010) Stereotactic radiosurgery for the management of brain metastases. N Engl J Med 362(12):1119–1127PubMedCrossRefGoogle Scholar
  3. 3.
    Jernal A, Murray T, Samuels A et al (2003) Cancer statistics. CA Cancer J Clin 53:5–26CrossRefGoogle Scholar
  4. 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 32:664–670PubMedCrossRefGoogle Scholar
  5. 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 29:701–704PubMedCrossRefGoogle Scholar
  6. 6.
    Schellinger PD, Meinck HM, Thron A (1999) Diagnostic accuracy of MRI compared to CCT in patients with brain metastases. J Neurooncol 44(3):275–281PubMedCrossRefGoogle Scholar
  7. 7.
    Fidler IJ, Yano S, Zhang RD et al (2002) The seed and soil hypothesis: vascularization and brain metastases. Lancet Oncol 3(1):53–57PubMedCrossRefGoogle Scholar
  8. 8.
    Hwang TL, Close TP, Grego JM et al (1996) Predilection of brain metastases in grey and white matter junction and vascular border zones. Cancer 77:1551–1555PubMedCrossRefGoogle Scholar
  9. 9.
    Paget S (1989) The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev 8:98–101PubMedGoogle Scholar
  10. 10.
    Delattre JY, Krol G, Thaler HT et al (1988) Distribution of brain metastases. Arch Neurol 45:741–744PubMedCrossRefGoogle Scholar
  11. 11.
    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):493–498PubMedCrossRefGoogle Scholar
  12. 12.
    Bender ET, Tomé WA (2011) Distribution of brain metastases: implications for non-uniform dose prescriptions. Br J Radiol 84(1003):649–658PubMedCrossRefGoogle Scholar
  13. 13.
    Hengel K, Sidhu G, Choi J et al (2012) Attributes of brain metastases from breast and lung cancer. Int J Clin Oncol (Epub ahead of print)Google Scholar
  14. 14.
    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):89–101PubMedCrossRefGoogle Scholar
  15. 15.
    Charil A, Zijdenbos AP, Taylor J et al (2003) Statistical mapping analysis of lesion location and neurological disability in multiple sclerosis: application to 452 patient data sets. NeuroImage 19(3):532–544PubMedCrossRefGoogle Scholar
  16. 16.
    Wen W, Sachdev PS (2004) Extent and distribution of white matter hyperintensities in stroke patients: the Sydney Stroke Study. Stroke 35(12):2813–2819PubMedCrossRefGoogle Scholar
  17. 17.
    Smith SM (2004) Overview of fMRI analysis. Br J Radiol 77(2):S167–75Google Scholar
  18. 18.
    Bates E, Wilson SM, Saygin AP et al (2003) Voxel-based lesion-symptom mapping. Nat Neurosci 6(5):448–450PubMedGoogle Scholar
  19. 19.
    Tzourio-Mazoyer N, Landeau B, Papathanassiou D et al (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15(1):273–289PubMedCrossRefGoogle Scholar
  20. 20.
    Tsukada Y, Fouad A, Pickren JW et al (1983) Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer 52:2349–2354PubMedCrossRefGoogle Scholar
  21. 21.
    Ghia A, Tomé WA, Thomas S et al (2007) Distribution of brain metastases in relation to the hippocampus: implications for neurocognitive functional preservation. Int J Radiat Oncol Biol Phys 68(4):971–977PubMedCrossRefGoogle Scholar
  22. 22.
    van der Sande JJ, van Tinteren H, Brandsma D et al (2009) Brain metastases in patients with pelvic or abdominal malignancy do not prevail in the posterior fossa: a retrospective study. J Neurol 256(9):1485–1487PubMedCrossRefGoogle Scholar
  23. 23.
    Hendrikse J, Petersen ET, van Laar PJ et al (2008) Cerebral border zones between distal end branches of intracranial arteries: MR imaging. Radiology 246:572–580PubMedCrossRefGoogle Scholar
  24. 24.
    Armulik A, Genové G, Mäe M et al (2010) Pericytes regulate the blood-brain barrier. Nature 468:557–561PubMedCrossRefGoogle Scholar
  25. 25.
    Carbonell WS, Ansorge O, Sibson N et al (2009) The vascular basement membrane as “soil” in brain metastasis. PLoS One 4(6):e5857PubMedCrossRefGoogle Scholar
  26. 26.
    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):2958–2971PubMedCrossRefGoogle Scholar
  27. 27.
    Lorger M, Krueger JS, O’Neal M, Staflin K et al (2009) Activation of tumor cell integrin alpha v beta 3 controls angiogenesis and metastatic growth in the brain. Proc Natl Acad Sci USA 106(26):10666–10671PubMedCrossRefGoogle Scholar
  28. 28.
    Bos PD, Zhang XH, Nadal C et al (2009) Genes that mediate breast cancer metastasis to the brain. Nature 459:1005–1009PubMedCrossRefGoogle Scholar
  29. 29.
    Hendrikse J, Van der Grond J, Lu H et al (2004) Flow territory mapping of the cerebral arteries with regional perfusion MRI. Stroke 35:882–887PubMedCrossRefGoogle Scholar
  30. 30.
    Van Laar PJ, Hendrikse J, Golay X et al (2006) In vivo flow territory mapping of major brain feeding arteries. NeuroImage 29:136–144PubMedCrossRefGoogle Scholar
  31. 31.
    Kajita Y, Takayasu M, Suzuki Y et al (1995) Regional differences in cerebral vasomotor control by nitric oxide. Brain Res Bull 38:365–369PubMedCrossRefGoogle Scholar
  32. 32.
    Iadecola C (1993) Regulation of the cerebral microcirculation during neural activity: Is nitric oxide the missing link? Trends Neurosci 16:206–15Google Scholar
  33. 33.
    Nozaki K, Moskowitz MA, Maynard KI et al (1993) Possible origins and distribution of immunoreactive nitric oxide synthetase-containing nerve fibers in cerebral arteries. J Cereb Blood Flow Metab 13:70–79PubMedCrossRefGoogle Scholar
  34. 34.
    Cavaglia M, Dombrowski SM, Drazba J et al (2001) Regional variation in brain capillary density and vascular response to ischemia. Brain Res 910:81–93PubMedCrossRefGoogle Scholar
  35. 35.
    Edvinsson L (1982) Vascular autonomic nerves and corresponding receptors in brain vessels. Pathol Biol (Paris) 30(5):261–268Google Scholar
  36. 36.
    Edvinsson L, Nielsen KC, Owman C et al (1972) Sympathetic neural influence on norepinephrine vasoconstriction in brain vessels. Arch Neurol 27:492–495PubMedCrossRefGoogle Scholar
  37. 37.
    Ito H, Yokoyama I, Iida H et al (2000) Regional differences in cerebral vascular response to PaCo2 changes in humans measured by positron emission tomography. J Cereb Blood Flow Metab 20:1264–1279PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Carlo Cosimo Quattrocchi
    • 1
    Email author
  • Yuri Errante
    • 1
  • Chiara Gaudino
    • 1
  • Carlo Augusto Mallio
    • 1
  • Alessandro Giona
    • 1
  • Daniele Santini
    • 2
  • Giuseppe Tonini
    • 2
  • Bruno Beomonte Zobel
    • 1
  1. 1.Unit of Radiology, CIR-Center for Integrated Research in Biomedicine and BioengineeringUniversity Campus Bio-Medico di RomaRomeItaly
  2. 2.Unit of Oncology, CIR-Center for Integrated Research in Biomedicine and BioengineeringUniversity Campus Bio-Medico di RomaRomeItaly

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