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Professor Yi Liang from the Department of Neurosurgery of Chongqing Daping Hospital summarized the imaging and histological characteristics and molecular mechanism of glioma invasion along the white matter tract.
and discuss the correlation of aggressive growth along white matter fiber bundles with glioma molecular typing, radiotherapy, and electric field therapy, the results of which were published online in Cancer Letters in February 2022
.
- Excerpted from the article chapter
【Ref: Wang J, et al.
Cancer Lett.
2022 Feb 1; 526:103-111.
doi: 10.
1016/j.
canlet.
2021.
11.
020.
Epub 2021 Nov 20.
】
Research background
Aggressive growth along the white matter fibrous bundle is a pathological feature of glioma and an important cause
of glioma surgical failure.
Professor Yi Liang from the Department of Neurosurgery of Chongqing Daping Hospital summarized the imaging and histological characteristics and molecular mechanism of glioma invasion along the white matter tract.
and discuss the correlation of aggressive growth along white matter fiber bundles with glioma molecular typing, radiotherapy, and electric field therapy, the results of which were published online in Cancer Letters in February 2022
.
Research methods
Invasive growth of glioma cells is mostly distributed along some specific anatomical structures, including perivascular spaces and white matter nerve fibers, and some glioma cells can travel along white matter nerve fibers to brain tissue 3-5 cm from the glioma margin, and even enter the contralateral brain tissue
through the corpus callosum.
The location and degree of destruction of white matter nerve fibers are closely related to the grade of glioma, and the ratio of white matter nerve fiber density index (FDi) near the tumor and FDi near the tumor to the FDi of the contralateral normal tissue (FDi ratio) in patients with high-grade glioma are significantly lower than those of low-grade glioma
.
White matter fibers adjacent to gliomas have significant demyelinating changes, while glioma patients with damaged structural integrity of white matter nerve fibers are prone to recurrence
.
Corticospinal tract, corpus callosum and other white matter fibers are destroyed by glioma and also affect the survival prognosis
of patients.
Study results
The principle of surgical treatment of glioma is to maximize the resection of the lesion with the least impairment of brain function, thereby improving the quality of
life of postoperative patients and prolonging median survival.
Current imaging tests are difficult to show the extent of glioma invasion along white matter nerve fibers, so it is very difficult
to determine the edge of glioma expansion.
At present, low-grade gliomas located in non-functional areas are mainly resected according to MRI-T2-Flair imaging; High-grade gliomas that are not functional areas are "excised" with an extension of about 2 cm based on MRI-T1 enhancement images, including tumor masses and peritumor edema areas
.
For functional area gliomas, only the MRI-T2-Flair imaging range is resected
in order to ensure the quality of life of patients after surgery as much as possible.
Due to the homotropic growth of high-grade gliomas, homofacial extension with "extended resection" is ideal; However, gliomas that invade along white matter nerve fibers often show the characteristics of anisotropic growth, and tumor cells may invade more rapidly in some directions than in other directions, so when the above method is used to determine the resection range or calculate the planning target volume (PTV) of postoperative radiotherapy, the treatment area will be greatly deviated
from the actual extent of the tumor.
MRI diffusion tensor imaging (DTI) is an effective non-invasive detection method to observe the structure and function of white matter bundles, which can realize the quantitative analysis
of the structural integrity of white matter nerve fibers.
DTI allows surgeons to obtain information about the specific orientation of the white matter nerve fibers in the brain
.
In 2013, Painter and Hillen developed glioma models based on tumor cell movement along the structure of white matter nerve fibers, clearly combining
the characteristic parameters of single-cell motility with the corresponding macroscopic model in a derivation pattern of scaled equations.
Now, clinicians can more precisely determine glioma boundary information
through DTI.
Quantitative parameters of DTI can also be used to assess glioma invasion behavior
along white matter nerve fibers.
DTI quantitative parameters refer to specific values used to measure the degree of dispersion of water molecules, including apparent diffusion coefficient (ADC), fractional anisotropy (FA), and axial diffusivity (AD) and radial diffusivity.
RD）
。
It is advantageous
to track the invasion status of gliomas along white matter nerve fibers with DTI direction and quantitative parameters.
However, due to the complexity of the tumor microenvironment and the differences in brain tissue components in specific brain regions, the clinical application of DTI parameters needs to be further explored
.
Gliomas often originate from gliacyte-rich white matter (Figure 1), with the frontotemporal lobe most commonly affected
.
Gliomas are not invaded locally but throughout the brain along white matter
.
Histopathological specific histopathological changes predominantly white matter nerve fiber damage are important features
of glioma invasion along white matter nerve fibers.
Most of the overall morphology of white matter nerve fibers in low-grade gliomas is basically complete, and white matter nerve fibers are mainly manifested as compression and shift, and a small part is interrupted; In high-grade glioma, white matter nerve fibers are mostly significantly damaged, mainly manifested as significant interruption and sparseness of white matter nerve fibers in the lesion area, and most patients can see that all or most of the white matter nerve fibers in the tumor area are interrupted
.
The degree of damage to white matter nerve fibers is also related
to the spatial distance of gliomas.
Qiu et al.
proposed the concept of effetive fibers of pyramidal tract (EPT), which indicates the number of pyramidal tracts that remain intact from the central anteroposterior walk back to the hind limbs of the internal capsule to the brain foot, reflecting the degree of influence of
the tumor on the pyramidal tract.
For gliomas with a high degree of malignancy, the extremely high aggressiveness seriously destroys EPT, and the scope of surgery should be appropriately expanded to reduce the recurrence rate of the tumor and prolong the recurrence time; For gliomas with a low degree of malignancy, when the EPT structure is not significantly destroyed and there is still limb function, attention should be paid to protecting the EPT around the tumor to reduce the postoperative disability rate and improve the quality of life of
patients after surgery.
Figure 1.
Histological features
of glioma.
Notch1-Sox9-Sox2 positive feedback loop, Wnt signaling pathway, TGF-β signaling pathway, gap junction protein 43, heat shock protein (HSP) family, RhoA-ROCK-SPARC signaling pathway, glioma-microglial network, glioma-neuronal network, etc.
in the tumor microenvironment may be involved in the molecular regulatory mechanism of glioma cell invasion along the white matter bundle
。
However, there is still a lack of an ideal in vitro model
for gliomas that invade along the white matter tract.
According to the gene expression profile, GBM can be divided into: proneural, mesenchymal, Mes, classic and Neural; Among them, preneuronal GSCs may be more likely to invade
along white matter nerve fibers.
The current study is insufficient to explain the recurrence pattern of radiotherapy accelerating the destruction of white matter nerve fibers into malignant gliomas, and whether the interference of electric fields on the electrical activity of nerve fibers also plays a role in further investigation
.
Figure 2.
Molecular mechanisms
of glioma invasion along the white matter bundle.
Conclusion of the study
In summary, it has been found that glioma cells have invaded along the white matter tract for 80 years, which is one of the most important pathological features of glioma, and it has also become a difficult problem
for glioma treatment.
In-depth understanding of the imaging and pathological characteristics of glioma invasion along white matter nerve fibers can help to more accurately delineate the scope of the tumor and perform precise surgical resection; Clarifying the specific mechanism of glioma invasion along white matter nerve fibers is helpful for the development of targeted interventions to inhibit the invasion of tumor single cells to distant sites
.
Of course, there are still many issues that need to be explored
.
