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- Roodakker, Kenney Roy, 1989-
(author)
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Towards new tools for clinical evaluation and visualization of tumor growth in patients with glioma
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Gliomas are derived from glial cells and are the most common type of primary brain tumors in adults. Gliomas are classified by the World Health Organization (WHO) according to their malignancy grade and histological and molecular features. Malignancy grades range from I to IV. WHO grade I tumors are benign tumors, mostly occurring in childhood. High-grade gliomas (WHO grades III and IV) are undifferentiated and fast-growing tumors, with glioblastoma being the most common and malignant form. Patients with glioblastomas have a median survival of only 15 months. Clinical outcomes vary, however, and markers are needed to assist in the decision-making process and management of these patients. PROX1 is a transcription factor critical for embryonic development, with a role in cell cycle control and progenitor cell differentiation. Apart from its role in normal central nervous system development, PROX1 has been ascribed both tumor suppressive and oncogenic roles in several human cancers. The role of PROX1 as a prognostic factor for survival in patients with glioblastomas was the focus of paper I.Gliomas WHO grade II, also called diffuse low-grade gliomas (DLGGs), are well-differentiated tumors that occur mainly in adult life, with a peak incidence at around 30–35 years of age and a median survival of 5–10 years. DLGGs grow continuously at a rate of a few mm per year and have a strong tendency to infiltrate the white matter tracts surrounding the tumor. Eventually these tumors transform into high-grade gliomas, but, as is the case with glioblastomas, there is a large variety of clinical outcomes. For radiological diagnosis, magnetic resonance imaging (MRI) is routinely used, often in combination with advanced MRI. Positron emission tomography with amino acid tracers provides additional diagnostic accuracy. From a histological as well as imaging point of view, DLGGs are heterogeneous tumors. The heterogeneity of DLGGs, in particular the correlation between radiological and histological tumor features, was the focus of paper II & paper III.Seizures are amongst the most common presenting symptoms of patients with gliomas. Seizure semiology in patients with brain tumors and other structural brain lesions is closely related to the anatomical location of the lesion and the involvement of functional networks. A possible dynamic interplay between the anatomical region of seizure onset and connected target areas within the network was the focus of paper IV.
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| 2. |
- Fahlström, Markus
(author)
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Perfusion MRI of the brain after radiotherapy in patients with glioblastoma – potential and problems
- 2018
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Licentiate thesis (other academic/artistic)abstract
- Perfusion Magnetic Resonance Imaging (MRI) is a useful tool in diagnostic evaluation and treatment response assessment in patients with glioblastoma. The standard treatment regimen includes surgical resection, radiotherapy and adjuvant chemotherapy. However, prognosis is poor; relative 5-year survival is 3–5%. Radiotherapy sequelae may have considerable negative effects on the patients’ quality of life. Acute and early delayed radiation-induced injury is primarily considered damage to the cerebral vascular tissue. The general aim of this study was to evaluate how perfusion MRI evaluation, based on contrast agent administration (DSC- and DCE-MRI), is affected by or can be useful to assess radiation-induced changes in normal appearing brain tissue in patients with glioblastoma after radiotherapy. Paper I: Dynamic Susceptibility Contrast (DSC)-MRI is a common perfusion MRI method in clinical practice in patients with glioblastoma. Due to inherent limitations, cerebral blood volume (CBV) and cerebral blood flow (CBF) derived from DSC-MRI are normalized to contralateral normal appearing white matter. Ten patients with glioblastoma were examined. Regional and global normalized CBV and normalized CBF in white and gray matter decreased after radiotherapy, followed by a tendency to recover. The response of nCBV and nCBF was dose-dependent in white matter but not in gray matter. In conclusion, radiotherapy effects on normal appearing white matter can confound treatment evaluation with DSC-MRI in patients with glioblastoma. Paper II: Dynamic Contrast Enhanced (DCE)-MRI may be useful in evaluating radiation-induced damage in normal appearing brain tissue. DCE-MRI-derived parameters, vascular permeability (Ktrans) and the fractional volume of the extravascular extracellular space (Ve) are potential biomarkers. Twelve patients with glioblastoma were examined. A tendency toward increased Ktrans and Ve was seen, suggesting that these parameters may act as potential biomarkers for acute and early delayed radiation-induced vascular damage
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