Giacomo Annio1,2, Robin Bugge3, Siri Fløgstad Svensson3, Omar Darwish4, Giorgio Seano5, Donata Biernat6, Karoline Skogen6, Jon Ramm-Pettersen 7, David Nordsletten8, Einar Vik-Mo 7, Katharina Schregel9, Kyrre Eeg Emblem3, and Ralph Sinkus1
1LVTS - U1148, University Paris, Paris, France, 2School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom, 3Department of Diagnostic Physics, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway, 4Department of Biomedical Engineering, King's College London, London, United Kingdom, 5U1021 INSERM, Institut Curie, Paris, France, 6Department of Radiology Ullevål, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway, 7Department of Neurosurgery, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway, 8Department of Biomedical Engineering and Cardiac Surgery, University of Michigan, Ann Arbor, MI, United States, 9Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany
Synopsis
Distinctive
traits of malignant tumours are abnormal angiogenesis and high pressure. Conventional magnetic resonance imaging (MRI)
plays a critical role in radiological evaluation of patients and tumour grading,
but challenges remain. Pressure and vasculature have a strong impact on the
tissue rheology and therefore they can be quantified by Magnetic Resonance
Elastography (MRE). We show that
MRE allows to quantify non-invasively tumour grade using pressure and tumour
vasculature through wave scattering. We believe that MRE could play a central
role in tumour grading and diagnosis as well as in therapy planning and dosage,
especially in multidrug treatments scenarios.
Introduction
It is well
understood that distinctive traits of malignant tumours are abnormal angiogenesis
[1], and high pressure [2-4]. These
conditions impair perfusion hence anticancer drugs efficacy [5-7] and lead to treatment
resistance and enhanced aggressiveness [8, 9]. Characterizing the tumour environment would be
crucial for patient management and for the evaluation of treatment effect [10]. Conventional MRI techniques play a critical role
in tumours diagnosis. However, challenges remain in the radiological evaluation
of patients and tumour grading, and current markers show contradictive
results [3,10].Currently, there is no method available to
quantify tumour pressure non-invasively [11], and although
various methods attempted a quantification of the vasculature organisation,
none of them is standardized clinically [12, 13]. In this work we used MRE and tissue
biomechanics to characterize tumour pressure and vasculature of a cohort of 26
patients with brain
tumours - 13 meningiomas, 13 gliomas (3 grade III and 10 grade IV). We show how
one MRE exam provides a comprehensive characterization of the tumour, providing
quantification of vascularization and tumour grading non-invasively (Figure 1a). Methods
Patients underwent MRI on a 3T scanner (Signa
Premier, GE Healthcare, Waukesha, WI) using a 48-channel head coil. A gravitational
transducer [14] placed underneath the
subject’s head was used to induce shear waves at 50 Hz into the brain. The MRE
acquisition was performed with a multishot gradient-echo MRE sequence using
Hadamard encoding [15]. Data inversion [16] allowed to calculate the complex
shear modulus G*=G’ +iG’’, where G’ is the shear stiffness, G’’ is the shear viscosity,
and Y=2/π*atan(Gl/Gd) in [0,1] is the phase angle. Previously, we
demonstrated that scattering is the main mechanism for wave attenuation. Therefore
Y offers a unique way to indirectly gauge local vasculature organization (Fig.1a)
[9, 10]. Furthermore, the retrieved tissue biomechanics was
used to compute the tumour pressure according to [19]. This method was extended
to be less sensitive to tumour boundary segmentation errors, introducing an
exhaustive parameter search through different tumour radii for finding a global
minimum in the search for the tumour pressure (Figure 1b). Results and discussion
Figure 2 (top) shows for the 26 patients
the correlation between tumours’ phase angle with their pressure. Firstly, the
phase angle allows to separate meningiomas from gliomas (Figure 2 bottom). This
observation is likely to be rooted in the origin of the wave attenuation in MRE
which is mainly scattering [17, 18].It is known that gliomas
exhibit a substantially different vascular organization than meningioma, which
could explain this difference in phase angle [19, 20].
Secondly, we observe that high
grade gliomas exhibit lower pressures than low grade gliomas. This measurement matches clinical experience: an
important feature reflecting the grade of gliomas is their ability to
infiltrate the brain parenchyma; this process starts within the vascular
network between the white matter tracts and subsequently spreads along the
commissural fibres. On the
contrary, more confined tumours as meningiomas exhibit elevated pressure, as
they commonly push away the brain parenchyma. . In general, the evolution towards a more
infiltrative phenotype is mirrored by a reduced amount of pressure exerted on
the surrounding, defining tumor pressure as a suitable way of grading tumours.Conclusions
The characterization of the tumour
microenvironment is crucial for tumour characterization and subsequent therapy
planning. In this abstract we show that through biomechanics one can assess non-invasively
tumour grade using pressure – high grade vs low grade gliomas - and tumour vasculature through wave scattering
i.e. phase angle – meningiomas vs gliomas. We believe that MRE could play a
central role in tumour grading and diagnosis as well as in therapy planning and
dosage, especially in multidrug treatments scenarios.Acknowledgements
No acknowledgement found.References
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