Abstract:The contribution of MRS(I) to the in vivo evaluation of cancer-metabolism-derived metrics, mostly since 2016, is reviewed here. Increased carbon consumption by tumour cells, which are highly glycolytic, is now being sampled by 13 C magnetic resonance spectroscopic imaging (MRSI) following the injection of hyperpolarized [1-13 C] pyruvate (Pyr). Hot-spots of, mostly, increased lactate dehydrogenase activity or flow between Pyr and lactate (Lac) have been seen with cancer progression in prostate (preclinical and… Show more
“…We have described the non-invasive assessment of response to therapy in preclinical GL261 GB (control and under TMZ therapy) with magnetic resonance spectroscopic imaging (MRSI) approaches. MRSI combines anatomical information from magnetic resonance imaging (MRI) [ 26 ], and magnetic resonance spectroscopy (MRS), which provides information regarding the metabolomic profile of the investigated tissue [ 27 , 28 , 29 ]. When using MRSI is coupled to advanced machine learning analysis (source extraction as described in [ 30 ]), spectral pattern differences between actively proliferating GB and GB responding to therapy can be shown colour-coded (the nosological images) in single-slice [ 23 ] or multislice volumetric approaches [ 24 ].…”
Glioblastomas (GB) are brain tumours with poor prognosis even after aggressive therapy. Previous work suggests that magnetic resonance spectroscopic imaging (MRSI) could act as a biomarker of efficient immune system attack onto GB, presenting oscillatory changes. Glioma-associated microglia/macrophages (GAMs) constitute the most abundant non-tumour cell type within the GB and can be polarised into anti-tumour (M1) or pro-tumour (M2) phenotypes. One of the mechanisms to mediate immunosuppression in brain tumours is the interaction between programmed cell death-1 ligand 1 (PD-L1) and programmed cell death-1 receptor (PD-1). We evaluated the subpopulations of GAMs in responding and control GB tumours to correlate PD-L1 expression to GAM polarisation in order to explain/validate MRSI-detected findings. Mice were evaluated by MRI/MRSI to assess the extent of response to treatment and with qPCR for GAMs M1 and M2 polarisation analyses. M1/M2 ratios and PD-L1 expression were higher in treated compared to control tumours. Furthermore, PD-L1 expression was positively correlated with the M1/M2 ratio. The oscillatory change in the GAMs prevailing population could be one of the key causes for the differential MRSI-detected pattern, allowing this to act as immune system activity biomarker in future work.
“…We have described the non-invasive assessment of response to therapy in preclinical GL261 GB (control and under TMZ therapy) with magnetic resonance spectroscopic imaging (MRSI) approaches. MRSI combines anatomical information from magnetic resonance imaging (MRI) [ 26 ], and magnetic resonance spectroscopy (MRS), which provides information regarding the metabolomic profile of the investigated tissue [ 27 , 28 , 29 ]. When using MRSI is coupled to advanced machine learning analysis (source extraction as described in [ 30 ]), spectral pattern differences between actively proliferating GB and GB responding to therapy can be shown colour-coded (the nosological images) in single-slice [ 23 ] or multislice volumetric approaches [ 24 ].…”
Glioblastomas (GB) are brain tumours with poor prognosis even after aggressive therapy. Previous work suggests that magnetic resonance spectroscopic imaging (MRSI) could act as a biomarker of efficient immune system attack onto GB, presenting oscillatory changes. Glioma-associated microglia/macrophages (GAMs) constitute the most abundant non-tumour cell type within the GB and can be polarised into anti-tumour (M1) or pro-tumour (M2) phenotypes. One of the mechanisms to mediate immunosuppression in brain tumours is the interaction between programmed cell death-1 ligand 1 (PD-L1) and programmed cell death-1 receptor (PD-1). We evaluated the subpopulations of GAMs in responding and control GB tumours to correlate PD-L1 expression to GAM polarisation in order to explain/validate MRSI-detected findings. Mice were evaluated by MRI/MRSI to assess the extent of response to treatment and with qPCR for GAMs M1 and M2 polarisation analyses. M1/M2 ratios and PD-L1 expression were higher in treated compared to control tumours. Furthermore, PD-L1 expression was positively correlated with the M1/M2 ratio. The oscillatory change in the GAMs prevailing population could be one of the key causes for the differential MRSI-detected pattern, allowing this to act as immune system activity biomarker in future work.
“…al. wherein they suggest that Lac/Bic might be a better metric for assessing cancer metabolism [18]. Prior cross-sectional hyperpolarized 13 C MRS studies demonstrated a consistent decrease in Lac/Bic ratios within three hours of anti-vascular endothelial growth factor (anti-VEGF) therapy in a glioblastoma (GBM) rodent model, with a spread in Lac/Bic values over the next 48 hrs suggesting this effect reverses at differential rates [19].…”
BackgroundMetabolism in tumor shifts from oxidative phosphorylation to inefficient glycolysis resulting in overproduction of lactate (Warburg effect), and cancers may be effectively treated if this imbalance were corrected. The aim of this longitudinal study of glioblastoma in a rat model was to determine whether the ratio of lactate (surrogate marker for glycolysis) to bicarbonate (for oxidative phosphorylation), as measured via in vivo magnetic resonance imaging of hyperpolarized 13C-labeled pyruvate accurately predicts survival.MethodsC6 Glioma implanted male Wistar rats (N = 26) were treated with an anti-vascular endothelial growth factor antibody B20.4.1.1 in a preliminary study to assess the efficacy of the drug. In a subsequent longitudinal survival study, magnetic resonance spectroscopic imaging (MRSI) was used to estimate [1-13C]Lactate and [1-13C]Bicarbonate in tumor and contralateral normal appearing brain of glioma implanted rats (N = 13) after injection of hyperpolarized [1-13C]Pyruvate at baseline and 48 hours post-treatment with B20.4.1.1.ResultsA survival of ~25% of B20.4.1.1 treated rats was noted in the preliminary study. In the longitudinal imaging experiment, changes in 13C Lactate, 13C Bicarbonate and tumor size measured at baseline and 48 hours post-treatment did not correlate with survival. 13C Lactate to 13C Bicarbonate ratio increased in all the 6 animals that succumbed to the tumor whereas the ratio decreased in 6 of the 7 animals that survived past the 70-day observation period.Conclusions13C Lactate to 13C Bicarbonate ratio (Lac/Bic) at 48 hours post-treatment is highly predictive of survival (p = 0.003). These results suggest a potential role for the 13C Lac/Bic ratio serving as a valuable measure of tumor metabolism and predicting therapeutic response.
“…For example, brain metabolism plays a major role in pathogenesis of some neurological disorders such as Alzheimer’s disease 17 - 19 by hypometabolismpromoted Aβ deposition. 20 Furthermore, the findings based on proton magnetic resonance spectroscopy have shown the alteration of metabolite concentration in various areas of the brain in different neurometabolic disorders such as multiple sclerosis, 21 brain tumors, 22 , 23 epilepsy, 24 , 25 Alzheimer disease, 26 - 28 and dementia 29 is significantly correlated with cognitive decline. Based on the abovementioned studies, metabolic diseases of the brain can lead to changes in the structure and function of brain areas associated with cognition; most metabolic diseases of the brain cause changes in neuronal structure and cognitive decline.…”
Section: Cognitive Changes In Metabolic Syndromementioning
Currently, metabolic syndrome has become a global health problem. Alterations in neurocognitive functions among patients with metabolic syndrome are important issues in this disorder. In this paper, studies on metabolic syndrome were reviewed and their importance emphasized for the benefit of experts and policy makers. Metabolic syndrome activates inflammatory mediators that disrupt brain metabolism. These mediators can be activated by metabolic inflammation and microvascular disorders and may further cause damage to the white matter and impair cognitive function. These alterations can result in serious changes in cognitive abilities. The association between cognitive changes and metabolic syndrome has been independently evaluated in several studies. In addition, some areas of research in the field of metabolic syndrome include the effectiveness of neurocognitive interventions to enhance normal behaviors or reduce risky behaviors in patients. Structural brain correlates of health-related behaviors provide a basis for designing more effective behavioral interventions by identifying the corresponding brain regions and using behavioral interventions.
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