Investigating the effect of multimodal therapy on white matter fibre density in glioma patients
Michel Friedrich, Ezequiel Farrher, Svenja Caspers, Philipp Lohmann, Christoph Lerche, Gabriele Stoffels, Christian P. Filss, Carolin Weiss Lucas, Maximilian I. Ruge, Karl-Josef Langen, Nadim J. Shah, Gereon R. Fink, Norbert Galldiks and Martin Kocher
14th November 2022
The treatment of gliomas is complex, and patients typically undergo a course of multimodal therapy which may include repeated tumour resection, irradiation, re-irradiation, and multiple courses of chemotherapy or targeted molecular therapy. Despite being essential for the treatment of glioma, it is known that these therapies, along with recurrent tumours, can lead to structural brain tissue damage; however, little is known about the impact of different types of damage on the fibre architecture of the affected white matter.
Based on a study of 121 glioma patients and a cohort of 121 healthy subjects, this work aimed to establish whether structural brain damage due to radiation or tumour recurrence, as indicated by pathologic MRI and FET PET findings, has a differential impact on local fibre density and the extent to which this affects the patient’s overall performance status to varying degrees.
Measurements were acquired from all patients using a 3T hybrid PET/MR scanner and anatomical and diffusion-weighted MR images along with FET PET images. The ECOG Performance Status Scale was used to assess the functioning level of each patient.
Healthy subjects were measured on a stand-alone MRI scanner (3T Siemens Tim-TRIO), identical to the MR component of the hybrid PET/MR system.
A recently developed modification of a widely used fibre-tracking method that allows for reasonable identification of the fibres passing through and near tumorous tissue and the surrounding brain structures was used to determine fibre quantity. The technique, known as single-shell 3-tissue CSD (SS3T-CSD), considers different tissue types from single-shell (single b-value plus non-diffusion weighted images) HARDI data and estimates the orientation of white matter fibres in a way that is as bias-free as possible, even within different compartments of a tumour.
The left side of the figure below shows that the tractography based on the diffusion model multi-shell multi-tissue constrained spherical deconvolution (MSMT-CSD) underestimates the fibres within the tumour area. In contrast, the single-shell 3-tissue CSD algorithm (SS3T) used in this work enabled the estimation of fibres even inside the tumour area (middle). In addition, the corresponding fibre density image can be seen on the right side.
FIGURE HERE
The results of the study suggest that, excluding resection cavities, a reduction in local fibre density is most significant in contrast-enhancing recurrent tumours, but total fibre loss induced by oedema or gliosis has an equally detrimental effect on the performance status of the patients due to the larger volume affected.
Although it remains unclear how the apparent loss of fibre density detected by MRI tractography methods is related to neuronal function, the data obtained from the study show that the overall extent of fibre loss in the volumes affected by different lesion types significantly affected the global performance status. Moreover, these results provide additional insight into the impact that treatment for gliomas can have on the fibre architecture of the brain, and it is hoped that this will further inform treatment planning in the future.
Origional Publication: Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients