MR Spectroscopic Evaluation of Brain Tissue Damage After Treatment for Pediatric Brain Tumors

Blamek, Sławomir; Larysz, Dawid; Ficek, K.; Sokół, Maria; Miszczyk, Leszek; Tarnawski, Rafał

doi:10.1007/978-3-211-98811-4_33

Cited by 10 publications

(4 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the expected immediate deleterious effects of CRT, a much more puzzling consequence is the ongoing long-term effects, which are still evident years or decades after treatment. For example, magnetic resonance spectroscopic analysis of children that have undergone CRT has demonstrated metabolic changes that are associated with brain tissue damage up to 18 months after completion of therapy ( Blamek et al, 2010 ). Magnetic resonance diffusion tensor imaging of adults 25 years after CRT has revealed loss of white matter integrity compared with healthy controls ( Schuitema et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

ADrosophilamodel to investigate the neurotoxic side effects of radiation exposure

Sudmeier

Howard

Ganetzky

2015

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Children undergoing cranial radiation therapy (CRT) for pediatric central nervous system malignancies are at increased risk for neurological deficits later in life. We have developed a model of neurotoxic damage in adult Drosophila following irradiation during the juvenile stages with the goal of elucidating underlying neuropathological mechanisms and of ultimately identifying potential therapeutic targets. Wild-type third-instar larvae were irradiated with single doses of γ-radiation, and the percentage that survived to adulthood was determined. Motor function of surviving adults was examined with a climbing assay, and longevity was assessed by measuring lifespan. Neuronal cell death was assayed by using immunohistochemistry in adult brains. We also tested the sensitivity at different developmental stages by irradiating larvae at various time points. Irradiating late third-instar larvae at a dose of 20 Gy or higher impaired the motor activity of surviving adults. A dose of 40 Gy or higher resulted in a precipitous reduction in the percentage of larvae that survive to adulthood. A dose-dependent decrease in adult longevity was paralleled by a dose-dependent increase in activated Death caspase-1 (Dcp1) in adult brains. Survival to adulthood and adult lifespan were more severely impaired with decreasing larval age at the time of irradiation. Our initial survey of the Drosophila Genetic Reference Panel demonstrated that differences in genotype can confer phenotypic differences in radio-sensitivity for developmental survival and motor function. This work demonstrates the usefulness of Drosophila to model the toxic effects of radiation during development, and has the potential to unravel underlying mechanisms and to facilitate the discovery of novel therapeutic interventions.

show abstract

Section: Discussionmentioning

confidence: 99%

ADrosophilamodel to investigate the neurotoxic side effects of radiation exposure

Sudmeier

Howard

Ganetzky

2015

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…MRI has been used in preclinical [ 12 ] and clinical [ 27 – 32 ] studies to diagnose and predict therapy outcomes for pediatric GBMs. The techniques most commonly used include in vivo 1 H magnetic resonance spectroscopy ( 1 H-MRS) [ 33 – 35 ], diffusion-weighted imaging (DWI) [ 36 ], and arterial spin labeling perfusion (ASL) [ 37 ]. 1 H-MRS has been used in research and clinical settings to measure metabolite levels in the brain, and is well suited to perform the diagnosis, characterization, and assessment of tumor response to treatment [ 38 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

et al. 2015

View full text Add to dashboard Cite

Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancerrelated deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals [(Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05)], as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.

show abstract

“…This clinical problem is, furthermore, of major importance within neurodiagnostics for children, as well as for the adult population. Specifically, a critical differential diagnostic dilemma in neuro-oncology is to distinguish non-tumorous cerebral hypoxia/ischemia from brain tumors [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39].…”

Section: Clinical Relevance Of the Studied Mrs Problemmentioning

confidence: 99%

Feasibility study for applying the lower-order derivative fast Padé transform to measured time signals

Belkić

2019

J Math Chem

View full text Add to dashboard Cite

Magnetic resonance spectroscopy (MRS), as a powerful and versatile diagnostic modality in physics, chemistry, medicine and other basic and applied sciences, depends critically upon reliable signal processing. It provides time signals by encoding, but cannot quantify on its own. Mathematical methods do so. The signal processor of choice for MRS is the fast Padé transform (FPT). The spectrum in the FPT is the unique polynomial quotient for the given Maclaurin expansion. The parametric FPT (parameter estimator) performs quantification of time signals encoded with MRS by explicitly solving the spectral analysis problem. Thus far, the non-parametric FPT (shape estimator) could not quantify. However, the non-parametric derivative fast Padé transform (dFPT) can quantify despite performing shape estimation alone. The dFPT was successfully benchmarked on synthesized MRS time signals for derivative orders ranging from 1 to 50. It simultaneously improved resolution (by splitting apart tightly overlapped peaks) and enhanced signal-to-noise ratio (by suppressing the background baseline). The same advantageous features of improving both resolution and signal-to-noise ratio are presently found to be upheld with encoded MRS time signals. Moreover, it is demonstrated that the dFPT hugely outperforms the derivative fast Fourier transform even for derivatives of orders as low as four. The clinical implications are discussed.

show abstract

MR Spectroscopic Evaluation of Brain Tissue Damage After Treatment for Pediatric Brain Tumors

Abstract: MRS examinations of uninvolved brain tissue indicate long-lasting metabolic disturbances. However, the NAA/Cr ratio increase may be a sign of at least partial recovery of metabolic function of the brain.

Cited by 10 publications

References 12 publications

ADrosophilamodel to investigate the neurotoxic side effects of radiation exposure

ADrosophilamodel to investigate the neurotoxic side effects of radiation exposure

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

Feasibility study for applying the lower-order derivative fast Padé transform to measured time signals

Contact Info

Product

Resources

About