The
aim of surgery in Neurooncology is to achieve maximal tumor cytoreduction while
avoiding postoperative neurological deficits. In order to achieve this goal it
is mandatory not only to preserve eloquent cortex but also to safeguard indispensable
white matter pathways. Intraoperative direct subcortical ESM is the method of
choice to map functional boundaries of the resection cavity and it has
significantly improved the survival rate of patients undergoing resection of
low-grade gliomas(1).
Diffusion
MR tractography has recently emerged as a valuable clinical tool for
presurgical planning(2-4) and
intraoperative imaging-guided navigation in the operating room(5). Diffusion MR
tractography has the potential to provide unique information about connectional
anatomy and pathology-induced changes. This information has not been available
before and it can be acquired with clinical 1.5 and 3 tesla MR units. Despite
several challenges and limitations inherent to current diffusion imaging
methods(6), the
information provided by tractography is good enough to be used in the clinic.
Currently tractography is a user-dependent method. The challenges, limitations
and pitfalls(7) must be
understood carefully before interpreting the results of tractography for
presurgical planning. Useful imperfect and user-dependent tests are used in the
clinic everyday all the time.
Diffusion MR
imaging provides unique insights into both macrostructure and microstructure.
Water molecules move preferentially along the bundle of parallel axon and
diffusion imaging reveals the dominant orientation of these bundles. In
the proximity of a tumor, white matter bundles can be displaced, infiltrated,
diluted by vasogenic edema, or destroyed(32). Diffusion
anisotropy is typically reduced in areas of tumor infiltration and/or vasogenic
edema. Preliminary validation studies of DTI MR tractography with
intraoperative ESM have shown that false negative results may be found in the
proximity of infiltrating low-grade glioma(33-35).
It is important to remark that tractograms are virtual
estimation (streamlines) of the orientation of white matter bundles. The
estimate depends on the microstructural properties of the tissue. The degree of
uncertainty of the estimate is reduced in anatomical and pathological
conditions: in voxels with more than one bundle (such as in the deep
fronto-parieto-temporal white matter at the crossroad between the corticospinal
tract, corpus callosum and SLF) and in voxels with increased free water content
secondary to tumor infiltration or edema leading to apparent reduced
anisotropy. The former type of challenge can be overcome with advanced
diffusion methods such as high angular resolution diffusion imaging (HARDI)(36) and constrained
spherical deconvolution (cSD)(37) which have the
ability to extract multiple orientations of fibers in voxels containing more
than one bundle. The latter type of challenge can be overcome with advanced
imaging methods able to separating diffusion properties of the bundles from
surrounding free water. Implementation of new advance methods such as Noddi(38), CHARMED(39), AxCaliber(40) and ActiveX(41) should offer a
new class of microstructural tissue parameters, such as mean axonal diameter,
that may give a more specific estimation of regional changes than measures
derived from DTI. In the future implementation of the new methods in the
clinics may have the potential to generate more reproducible, less user-defined
tract reconstruction in patients with glioma.
Several important issues are the focus of current basic
and clinical research: function, importance, vulnerability and indispensability
of each pathway in reference to network functionality. Gliomas infiltrating the
perisylvian region on the dominant hemisphere offer a unique opportunity to
identify gray and white matter structures that are essential for speech
production. In a study on 19 right-handed patients it was shown that gliomas
growing in the ventrolateral aspect of the left frontal lobe may cause mild to
moderate speech deficits. Gliomas growing in the left VPCG were much more
likely to cause speech deficits than gliomas infiltrating the IFG, including
Broca area. MR DTI tractography was valuable to demonstrate that lesion
extension to the AF was a requisite for the appearance of aphasia in brain
tumor patients(42). Patients with
glioma infiltrating either the IFG or the VPCG without involvement of the
AF-direct segment did not show conduction aphasia.
A prominent role for the insula in speech production has
been suggested by an MRI study in 25 stroke patients with a deficit in motor
planning of articulatory movements(27). All patients
with the deficit had lesions that included a discrete region of the dominant
precentral gyrus of the insula, but not all had a lesion in pars opercularis.
This area was completely spared in other 19 stroke patients without these
articulation deficit. fMRI studies have confirmed the important role of the
insula for motor planning of speech. However, patients with diffuse LGG
infiltrating the insula, the temporal stem and the anterior temporal region
have normal scores on language tests despite large tumor size.
In conclusion, fMRI and DTI provide unique information
that has been changing presurgical evaluation of patients with brain gliomas,
and in particular when the mass is located nearby eloquent areas. Virtual
dissection of the major white matter tracts should be used only as a road map
for presurgical planning and as guidance for intraoperative subcortical ESM.
Clinical studies with MR
diffusion tractography are showing that lesion extention to the white matter
pathways (i.e. AF and IFOF) connecting frontal to parietal and temporal speech regions
is an important mechanism for the appearance of aphasia.
More advanced diffusion imaging methods such as Noddi and
Spherical Deconvolution are being implemented to meet the challenges of
presurgical planning in patients with a brain tumor.
References
1. Duffau H.
Lessons from brain mapping in surgery for low-grade glioma: insights into
associations between tumour and brain plasticity. Lancet Neurol.
2005;4(8):476-86. Epub 2005/07/22.
2. Clark CA,
Barrick TR, Murphy MM, Bell BA. White matter fiber tracking in patients with
space-occupying lesions of the brain: a new technique for neurosurgical
planning? Neuroimage. 2003;20(3):1601-8.
3. Field AS,
Alexander AL, Wu YC, Hasan KM, Witwer B, Badie B. Diffusion tensor eigenvector
directional color imaging patterns in the evaluation of cerebral white matter
tracts altered by tumor. J Magn Reson Imaging. 2004;20(4):555-62.
4. Mori S,
Frederiksen K, van Zijl PC, Stieltjes B, Kraut MA, Solaiyappan M, et al. Brain
white matter anatomy of tumor patients evaluated with diffusion tensor imaging.
Ann Neurol. 2002;51(3):377-80.
5. Nimsky C,
Ganslandt O, Hastreiter P, Wang R, Benner T, Sorensen AG, et al. Intraoperative
diffusion-tensor MR imaging: shifting of white matter tracts during neurosurgical
procedures--initial experience. Radiology. 2005;234(1):218-25.
6. Jones DK.
Studying connections in the living human brain with diffusion MRI. Cortex.
2008;44(8):936-52. Epub 2008/07/19.
7. Jones DK,
Cercignani M. Twenty-five pitfalls in the analysis of diffusion MRI data. NMR
Biomed. 2010;23(7):803-20. Epub 2010/10/05.
8. Mesulam MM.
Defining Neurocognitive Networks in the BOLD New World of Computed
Connectivity. Neuron. 2009;62:1-3.
9. Catani M,
Dell'acqua F, Bizzi A, Forkel SJ, Williams SC, Simmons A, et al. Beyond
cortical localization in clinico-anatomical correlation. Cortex.
2012;48(10):1262-87. Epub 2012/09/22.
10. Hickok
G, Poeppel D. Dorsal and ventral streams: a framework for understanding aspects
of the functional anatomy of language. Cognition. 2004;92(1-2):67-99. Epub
2004/03/24.
11. Hickok
G, Poeppel D. The cortical organization of speech processing. Nat Rev Neurosci.
2007;8(5):393-402. Epub 2007/04/14.
12. Weiller
C, Bormann T, Saur D, Musso M, Rijntjes M. How the ventral pathway got lost:
and what its recovery might mean. Brain Lang. 2011;118(1-2):29-39. Epub
2011/03/25.
13. Petrides
M, Pandya DN. Association fiber pathways to the frontal cortex from the
superior temporal region in the rhesus monkey. J Comp Neurol. 1988;273:52– 66.
14. Catani
M, Jones DK, ffytche DH. Perisylvian language networks of the human brain. Ann
Neurol. 2005;57(1):8-16.
15. Lawes
IN, Barrick TR, Murugam V, Spierings N, Evans DR, Song M, et al. Atlas-based
segmentation of white matter tracts of the human brain using diffusion tensor
tractography and comparison with classical dissection. Neuroimage.
2008;39(1):62-79.
16. Catani
M, Mesulam M. The arcuate fasciculus and the disconnection theme in language
and aphasia: history and current state. Cortex. 2008;44(8):953-61. Epub
2008/07/11.
17. Weiller
C, Musso M, Rijntjes M, Saur D. Please don't underestimate the ventral pathway
in language. Trends Cogn Sci. 2009;13(9):369-70; 70-1. Epub 2009/09/01.
18. Saur
D, Kreher BW, Schnell S, Kummerer D, Kellmeyer P, Vry MS, et al. Ventral and
dorsal pathways for language. Proc Natl Acad Sci U S A. 2008;105(46):18035-40.
Epub 2008/11/14.
19. Bizzi
A. Presurgical Mapping of Verbal Language in Brain Tumors with Functional MR
Imaging and MR Tractography. In: Pia Sundgren M, editor. Advanced Imaging
Techniques in Brain Tumors: Elsevier; 2009. p. 573-96.
20. Kier
EL, Staib LH, Davis LM, Bronen RA. MR imaging of the temporal stem: anatomic
dissection tractography of the uncinate fasciculus, inferior occipitofrontal
fasciculus, and Meyer's loop of the optic radiation. AJNR Am J Neuroradiol.
2004;25(5):677-91. Epub 2004/05/14.
21. Catani
M, Thiebaut de Schotten M. A diffusion tensor imaging tractography atlas for
virtual in vivo dissections. Cortex. 2008;44(8):1105-32.
22. de
Schotten MT, Ffytche DH, Bizzi A, Dell'Acqua F, Allin M, Walshe M, et al.
Atlasing location, asymmetry and inter-subject variability of white matter
tracts in the human brain with MR diffusion tractography. Neuroimage.
2011;54(1):49-59. Epub 2010/08/05.
23. Catani
M, Howard RJ, Pajevic S, Jones DK. Virtual in vivo interactive dissection of
white matter fasciculi in the human brain. Neuroimage. 2002;17(1):77-94.
24. Dejerine
J, Dejerine-Klumpke A. Anatomies des centres nerveux. Paris: Rueff et Cie;
1895.
25. Papagno
C, Miracapillo C, Casarotti A, Romero Lauro LJ, Castellano A, Falini A, et al.
What is the role of the uncinate fasciculus? Surgical removal and proper name
retrieval. Brain. 2010. Epub 2010/10/21.
26. Petrides
M, Pandya DN. Distinct parietal and temporal pathways to the homologues of
Broca's area in the monkey. PLoS Biol. 2009;7(8):e1000170. Epub 2009/08/12.
27. Dronkers
NF. A new brain region for coordinating speech articulation. Nature.
1996;384(6605):159-61. Epub 1996/11/14.
28. Duffau
H, Gatignol P, Mandonnet E, Peruzzi P, Tzourio-Mazoyer N, Capelle L. New
insights into the anatomo-functional connectivity of the semantic system: a
study using cortico-subcortical electrostimulations. Brain. 2005;128(Pt
4):797-810.
29. Bello
L, Gallucci M, Fava M, Carrabba G, Giussani C, Acerbi F, et al. Intraoperative
subcortical language tract mapping guides surgical removal of gliomas involving
speech areas. Neurosurgery. 2007;60(1):67-82.
30. Mandonnet
E, Nouet A, Gatignol P, Capelle L, Duffau H. Does the left inferior
longitudinal fasciculus play a role in language? A brain stimulation study.
Brain. 2007;130(Pt 3):623-9.
31. Shinoura
N, Suzuki Y, Tsukada M, Yoshida M, Yamada R, Tabei Y, et al. Deficits in the
left inferior longitudinal fasciculus results in impairments in object naming.
Neurocase.16(2):135-9. Epub 2009/11/26.
32. Jellison
BJ, Field AS, Medow J, Lazar M, Salamat MS, Alexander AL. Diffusion tensor
imaging of cerebral white matter: a pictorial review of physics, fiber tract
anatomy, and tumor imaging patterns. AJNR Am J Neuroradiol. 2004;25(3):356-69.
Epub 2004/03/24.
33. Bello
L, Gambini A, Castellano A, Carrabba G, Acerbi F, Fava E, et al. Motor and
language DTI Fiber Tracking combined with intraoperative subcortical mapping
for surgical removal of gliomas. Neuroimage. 2008;39(1):369-82. Epub
2007/10/04.
34. Leclercq
D, Duffau H, Delmaire C, Capelle L, Gatignol P, Ducros M, et al. Comparison of
diffusion tensor imaging tractography of language tracts and intraoperative
subcortical stimulations. J Neurosurg. 2010;112(3):503-11. Epub 2009/09/15.
35. Spena
G, Nava A, Cassini F, Pepoli A, Bruno M, D'Agata F, et al. Preoperative and
intraoperative brain mapping for the resection of eloquent-area tumors. A
prospective analysis of methodology, correlation, and usefulness based on
clinical outcomes. Acta Neurochir (Wien). 2010;152(11):1835-46. Epub
2010/08/24.
36. Berman
JI, Chung S, Mukherjee P, Hess CP, Han ET, Henry RG. Probabilistic streamline
q-ball tractography using the residual bootstrap. Neuroimage. 2008;39(1):215-22.
Epub 2007/10/04.
37. Tournier
JD, Calamante F, Connelly A. Robust determination of the fibre orientation
distribution in diffusion MRI: non-negativity constrained super-resolved
spherical deconvolution. Neuroimage. 2007;35(4):1459-72. Epub 2007/03/24.
38. Zhang
H, Schneider T, Wheeler-Kingshott CA, Alexander DC. NODDI: practical in vivo
neurite orientation dispersion and density imaging of the human brain.
Neuroimage. 2012;61(4):1000-16. Epub 2012/04/10.
39. Assaf
Y, Basser PJ. Composite hindered and restricted model of diffusion (CHARMED) MR
imaging of the human brain. Neuroimage. 2005;27(1):48-58. Epub 2005/06/28.
40. Assaf
Y, Blumenfeld-Katzir T, Yovel Y, Basser PJ. AxCaliber: a method for measuring
axon diameter distribution from diffusion MRI. Magn Reson Med.
2008;59(6):1347-54. Epub 2008/05/29.
41. Zhang
H, Hubbard PL, Parker GJ, Alexander DC. Axon diameter mapping in the presence
of orientation dispersion with diffusion MRI. Neuroimage. 2011;56(3):1301-15.
Epub 2011/02/15.
42. Bizzi
A, Nava S, Ferre F, Castelli G, Aquino D, Ciaraffa F, et al. Aphasia induced by
gliomas growing in the ventrolateral frontal region: assessment with diffusion
MR tractography, functional MR imaging and neuropsychology. Cortex.
2012;48(2):255-72. Epub 2012/01/13.