Title: DTI tractography in brain tumour patients with headache and non-headache
phenotype
- Background
The brainmade up of two variety of tissues “Gray matter” and “White Matter”. The white
matter medulla lies below the Gray matter cortex containing millions of neuronal
axons(Fields, 2010). These fibres are divergent constituting 50% of volume of adult brain and
link neurons located in various functional areas of the brain(Filley, 2022; Yu, Lin, Liu, & Li,
2020). The tracts are enveloped with myelin sheet propagating fast electrical impulses.
Disarrangement of these neuronal fibres causes impairment of neurons, disturbance in
mediating nerve impulses and loss of myelin sheet hastening dysfunction(Bergstrom et al.,
1986; O’Brien et al., 1987). Brain tumours like glioblastoma are space occupying lesions
which displace or infiltrate the white matter fibres. These tumours traverse the neural tract
like corticospinal tract, inferior longitudinal fasciculus and anterior thalamic radiations
leading to drop-in overall survival rate(Mickevicius et al., 2015). An individual with brain
The headache in brain tumour is recorded
in 31% to 71% of patients (Vazquez‐Barquero et al, 1994). The brain tumour headaches are
associated with various neurological deficits like seizures, nausea, vomiting, change in
individuality, blurring of vision and papilledema (Christiaans et al, 2002, Loghin and Levin,
2006). In the absence of intracranial pressure, the brain tumour headaches are placid and less
likely to cause associated neurological symptoms. A headache with a diversification mimics
an underlying brain tumour. The neurological deficits can be prevented by preoperative
interventions before opting for a neurosurgery procedure. Magnetic resonance imaging (MRI)
is a non-invasive technique appropriate in ruling out, handling, and forecasting prognosis of
brain tumours preventing an individual from hazardous radiation exposure. However, the
structural MRI is fails to identify the white matter fibres(Pujol, 2015).
Diffusion tensor imaging is one of the crucial modalities of MRI which conceptualize the white matter tract focusing on connectivity of the tumour with the neighbouring brain tissue(Basser &
Pierpaoli, 1998). The principle of DTI is established on anisotropic water movement along
the white matter which is unrestricted down the tracts and restricted perpendicular to the
tract. It assist in expressing fibre arrangement on a pixel by pixel ground and measure the
movement anisotropy known as functional anisotropy (FA)(Lim & Helpern, 2002; Sotak,
2002; Takahashi et al., 2002). In the present situation, preoperative DTI tractography of the
white matter tract is necessary to provide a 3D visualization of the white matter fibres to
understand the anatomical location, asymmetry and variability in relations to the brain
tumours that will assist the neurosurgeons in carrying out their procedures in crucial areas of
the brain cortex. A quantifiable data demonstrating altered diffusion figures with details of
orientation through Directionally encoded colour (DEC) maps will be taken which will guide
the surgeons with significant clinical information by tracking the position and durability of
the peritumoural fibres adjacent to the tumours. Therefore, this study will emphasize on
investigation and interpretation of fractional (FA) anisotropic changes and mean diffusivity
(MD) by tractography of white matter fibres in brain tumour patients in connection with
headache and non-headache phenotype.
- Review of literature
A patient with a brain tumour will show specific indications or symptoms, and a new
complaint of headache is always causing concern for both the patient and the doctor. A
decision to evaluate the headache is critical because it involves a number of issues, including
time therapeutic value, clinical confidence, and limits. By ruling out any underlying
pathology, the neuroimaging of the brain tumour patient will instil confidence in clinicians
(Kernick et al, 2008). Magnetic resonance imaging (MRI) modalities play a critical role in
non-invasive techniques for detecting brain tumours linked with headache (Chiang et al,
4
2018).
Diffusion tensor imaging (DTI) is a technique that assesses the microstructural
solidarity of brain tissue. It can be utilised to examine the tissue integrity of white matter
(WM) tracts in particular(Richter, Woernle, Krayenbühl, Kollias, & Bellut, 2015). Fractional
anisotropy (FA) is a scalar (range 0–1) that describes how anisotropic the diffusion is. When
the diffusion is same in all direction it is isotropic with FA value of 0, as in cerebrospinal
fluid. Consequently, when diffusion occurs along one axis, an FA value of 1 is present. The
overall non-directional diffusion across the WM tract is measured by mean diffusivity (MD),
axonal diffusivity (AD), and radial diffusivity (RD), which is measured perpendicular to
AD(Kattem Husøy, Eikenes, Håberg, Hagen, & Stovner, 2019). Because water diffusion
parallel to fibre tracts is less restricted than diffusion perpendicular to fibre tracts, FA in
white matter is high(Pierpaoli, Jezzard, Basser, Barnett, & Di Chiro, 1996). Variations in the
FA in different parts of the brain have been linked to the intensity of depressive symptoms
(Blood et al., 2010). Furthermore, Afferent and efferent fibre abnormalities from the medial
prefrontal and orbitofrontal cortex, as well as the thalamus, are closely linked to the onset of
depression symptoms aggravating headache(Price & Drevets, 2010). In patients with
headache, the mean number of hyperintensities in extremely acute pain increased with wide
white matter hyperintensities increased considerably with growing pain intensity during the
attack(Negm, Housseini, Abdelfatah, & Asran, 2018). Previous studies showed that
decreasing the fractional anisotropy (FA) threshold could boost tracking in tumours and
oedema(Akai et al., 2005). With reference to individual’s 3-dimensional brain architecture,
white matter tractography (WMT) offers a useful complementary technique for studying the
optic tract-optic radiation (OR) and the Meyer loop structure in vivo(Wu et al., 2012). WMT
offers useful neuropsychological prognostic information that might assist with patient
counselling before planning treatment(McDonald et al., 2008). Cortical and subcortical brain
regions can be impacted with headache or with a single seizure centre because of coordinated
5
neuronal firing through neural networks(Thivard et al., 2005). Hence, Evaluation of the white
matter tracts that connect these diverse locations may therefore be able to provide light on the
generalised alterations in the brain associated with headache and non-headache phenotypes in
brain tumour patients.
- Problem statement
A brain tumour is one of the most commonly feared causes of headache, and many
individuals come with an underlying tumour (Goffaux & Fortin, 2010). Other neurological
manifestations of a brain tumour headache include altered personality, nausea, vomiting, and
blurred vision. (Christiaans, Kelder, Arnoldus, & Tijssen, 2002). However, it is possible that
the mechanism causing headache in patients with brain tumours is in some way tied to the
process that causes primary headache (Kuntz et al., 1992). One of the most important
imaging methods for detecting brain tumours is MRI. It provides ideal data for deciding and
planning treatment by observing management efficacy and anticipating a favourable
prognosis. Traditional structural MRI, on the other hand, has a limited ability to distinguish
between two types of intra-cerebral tumours since they appear to be the same(Server et al.,
2010).
White matter tractography (WMT) is a technique for spatially analyzing the white matter of
the brain(Essayed et al., 2017). There are reports of connection between ischemic stroke and
white matter hyperintensities in studies of headaches. Consequently, more hypertintense areas
are evidenced in tensor type of headache. Diffusion tensor imaging (DTI) has been used to
investigate the link between headache and White matter microstructure, but mainly in small
clinic-based samples(Ellerbrock, Engel, & May, 2013). At present no studies have been
reported with secondary headache and white matter tractography. The goal of this study is to
look into the microstructure of white matter in brain tumour patients with headache and nonheadache phenotype. Tract volumes and tract-average values of DTI indices will be acquired
6
with tractography and will be compared between phenotypes to see if potential regional
differences in white matter microstructure may be reflected at the level of white matter (WM)
tracts.
Articles website
- https://www.researchgate.net/publication/50850000_An_Introduction_to_Diffusion_Tensor_Image_Analysis