1H MR spectroscopy of inflammation, infection and ischemia of the brain

Mader, Irina; Rauer, Sebastian; Gall, Peter; Klose, Uwe

doi:10.1016/j.ejrad.2008.02.033

Cited by 105 publications

(69 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As with ventricular enlargement, however, hyperintensities noted on T2-weighted scans are nonspecific and reflect several different tissue processes including, but not limited to, edema, cellular infiltration, gliosis, demyelination, and severe necrosis (Pirko and Johnson, 2008). Finally, in agreement with previous studies in thiamine deficiency (Lee et al, 2001; Lee et al, 1995; Mascalchi et al, 2002; Murata et al, 2001; Pfefferbaum et al, 2007; Rose et al, 1993), but in contradiction to findings in neuroinflammatory diseases showing elevations in Cho (Inglese et al, 2003; Mader et al, 2008; Valcour et al, 2012), MRS in the thalamus detected lower NAA and lower Cho levels following thiamine deficiency. Since thiamine deficiency is associated with neuroinflammation (Beauchesne et al, 2009; Calingasan and Gibson, 2000; Ke and Gibson, 2004; McRee et al, 2000; Meng and Okeda, 2003; Nixon et al, 2008), this result suggests that Cho is not a selective marker for neuroinflammation (Chang et al, 2013; Mader et al, 2008).…”

Section: Discussionsupporting

confidence: 91%

“…In a model of hydrocephalus, ventricular enlargement was associated with increased expression of GFAP (a marker of astrocytosis) and Iba-1 (a marker of microgliosis)(Xu et al, 2012). MRS in neuroinflammatory conditions such as multiple sclerosis and HIV typically identifies a pattern of reduced levels of N-acetyl aspartate (NAA, a marker of neuronal integrity) (Rigotti et al, 2012; Schweinsburg et al, 2005), elevated levels of choline-containing compounds (Cho, a marker of cell-membrane metabolism and cellular turnover) (Inglese et al, 2003; Mader et al, 2008; Valcour et al, 2012), and elevated levels of myo-Inositol (mI, a putative glial marker) (Bagory et al, 2012; Fernando et al, 2004; Harezlak et al, 2011; Kirov et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Associations between in vivo neuroimaging and postmortem brain cytokine markers in a rodent model of Wernicke's encephalopathy

Zahr

Alt

Mayer

et al. 2014

Experimental Neurology

View full text Add to dashboard Cite

Thiamine (vitamin B1) deficiency, associated with a variety of conditions, including chronic alcoholism and bariatric surgery for morbid obesity, can result in the neurological disorder Wernicke’s encephalopathy (WE). Recent work building upon early observations in animal models of thiamine deficiency has demonstrated an inflammatory component to the neuropathology observed in thiamine deficiency. The present, multilevel study including in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS) and postmortem quantification of chemokine and cytokine proteins sought to determine whether a combination of these in vivo neuroimaging tools could be used to characterize an in vivo MR signature for neuroinflammation. Thiamine deficiency for 12 days was used to model neuroinflammation; glucose loading in thiamine deficiency was used to accelerate neurodegeneration. Among 38 animals with regional brain tissue assayed postmortem for cytokine/chemokine protein levels, three groups of rats (controls+glucose, n=6; pyrithiamine+saline, n=5; pyrithiamine+glucose, n=13) underwent MRI/MRS at baseline (time 1), after 12 days of treatment (time 2), and 3h after challenge (glucose or saline, time 3). In the thalamus of glucose-challenged, thiamine deficient animals, correlations between in vivo measures of pathology (lower levels of N-acetyle aspartate and higher levels of lactate) and postmortem levels of monocyte chemotactic protein-1 (MCP-1, also known as chemokine ligand 2, CCL2) support a role for this chemokine in thiamine deficiency-related neurodegeneration, but do not provide a unique in vivo signature for neuroinflammation.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Associations between in vivo neuroimaging and postmortem brain cytokine markers in a rodent model of Wernicke's encephalopathy

Zahr

Alt

Mayer

et al. 2014

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…Alternatively, it is possible that (i) longer EtOH exposure protocols (e.g., Valles et al, 2004), (ii) higher BALs (e.g., Knapp and Crews, 1999), (iii) models of intermittent EtOH exposure (e.g., Qin et al, 2008), (iv) different sampling times, or (v) different species or strains are necessary to observe changes in the levels of circulating, liver, or brain cytokines. Optional interpretations for the increase in Cho that need to be explored include but are not limited to demyelination (Mader et al, 2008) or cell membrane disruption because of changes in the contributions of free Cho, phosphocholine, or glycerophosphocholine on the MRS-detectable Cho signal (Griffin et al, 2001; Le Bourhis et al, 1986). …”

Section: Resultsmentioning

confidence: 99%

Measurement of Serum, Liver, and Brain Cytokine Induction, Thiamine Levels, and Hepatopathology in Rats Exposed to a 4‐Day Alcohol Binge Protocol

Zahr

Luong

Sullivan

et al. 2010

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

Background In rodent and human studies, ethanol (EtOH) exposure is associated with elevated brain levels of the magnetic resonance spectroscopy (MRS) signal representing choline-containing compounds (Cho). One interpretation of elevated brain Cho is that it is a marker of neuroinflammation, and some evidence suggests that EtOH exposure promotes neuroinflammation. This study aimed to determine whether binge EtOH exposure (intragastric 3 g/kg 25% EtOH every 8 hours for 4 days) would induce the expression of certain cytokines in blood, liver, or brain, thereby supporting the neuroinflammation hypothesis of elevated Cho. Methods Ten of 18 wild-type male Wistar rats (~322 g at baseline) were exposed to EtOH and attained average blood alcohol levels of ~315 mg/dl across 4 days. Blood for cytokine immunoassays was collected at baseline, after 5 doses of EtOH (binge), and immediately preceding euthanasia either 4 or 24 hours after the last dose of EtOH. Blood was additionally assayed for the levels of thiamine and liver enzymes; liver histopathology was performed postmortem; and tissue from liver and 6 brain regions was assayed for the potential induction of 7 cytokines. Results There were no group effects on the levels of thiamine or its phosphate derivatives, thiamine monophosphate or thiamine diphosphate. ANOVAs of liver enzyme levels indicated that only alkaline phosphatase (ALP) levels were higher in the EtOH group than in control group at binge; ALP elevations, however, are difficult to explain in the absence of changes in the levels of additional liver enzymes. Postmortem liver pathology provided evidence for minimal microvesicular lipidosis and portocentric fibrosis in the EtOH group. Group effects on the levels of the measured cytokines in the blood (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-13, and GRO/CXCL1) were not significant. Similarly, postmortem evaluation of liver cytokines did not reveal group effects. Postmortem evaluation of the 7 cytokines in 6 brain regions (anterior cerebellar vermis, cingulate cortex, frontal cortex, hippocampus, hypothalamus, striatum) also failed to identify group effects. Conclusions A single 4-day bout of binge EtOH exposure alone was insufficient to induce the expression of 7 cytokines in blood, liver, or 6 brain regions of wild-type Wistar rats. Alternative interpretations for elevations in brain Cho in response to a 4-day binge EtOH treatment are therefore necessary and may include induction of cytokines not measured herein or other non-inflammatory mechanisms.

show abstract

“…This was explained by the increased cell density of astrocytic origin in these tumors. Increased MI concentrations have also been assessed as marker for astrocytic gliosis in diseases like gliomatosis cerebri or multiple sclerosis, usually being accompanied by changes in creatine (Cre) and other metabolites [19,20]. In the context of glioblastoma MI levels in the tumor are lower than in normal appearing tissue [21–25].…”

Section: Introductionmentioning

confidence: 99%

Myoinositol as a Biomarker in Recurrent Glioblastoma Treated with Bevacizumab: A 1H-Magnetic Resonance Spectroscopy Study

et al. 2016

View full text Add to dashboard Cite

BackgroundAntiangiogenic treatment of glioblastomas with Bevacizumab lacks predictive markers. Myoinositol (MI) is an organic osmolyte, with intracellular concentration changes depending on the extracellular osmolality. Since Bevacizumab markedly reduces tumor edema and influences the tumor microenvironment, we investigated whether the MI concentration in the tumor changes during therapy.MethodsWe used 1H-magnetic resonance spectroscopy to measure the MI concentrations in the tumor and contralateral control tissue of 39 prospectively recruited patients with recurrent glioblastomas before and 8–12 weeks after starting therapy. 30 patients received Bevacizumab and 9 patients were treated with CCNU/VM26 as control. We performed a survival analysis to evaluate MI as a predictive biomarker for Bevacizumab therapy.ResultsMI concentrations increased significantly during Bevacizumab therapy in tumor (p < .001) and control tissue (p = .001), but not during CCNU/VM26 treatment. For the Bevacizumab cohort, higher MI concentrations in the control tissue at baseline (p = .021) and higher differences between control and tumor tissue (delta MI, p = .011) were associated with longer survival. A Kaplan-Meier analysis showed a median OS of 164 days for patients with a deltaMI < 1,817 mmol/l and 275 days for patients with a deltaMI > 1,817 mmol/l. No differences were observed for the relative changes or the post treatment concentrations. Additionally calculated creatine concentrations showed no differences in between subgroups or between pre and post treatment measurements.ConclusionOur data suggest that recurrent glioblastoma shows a strong metabolic reaction to Bevacizumab. Further, our results support the hypothesis that MI might be a marker for early tumor cell invasion. Pre-therapeutic MI concentrations are predictive of overall survival in patients with recurrent glioblastoma treated with Bevacizumab.

show abstract

1H MR spectroscopy of inflammation, infection and ischemia of the brain

Cited by 105 publications

References 67 publications

Associations between in vivo neuroimaging and postmortem brain cytokine markers in a rodent model of Wernicke's encephalopathy

Associations between in vivo neuroimaging and postmortem brain cytokine markers in a rodent model of Wernicke's encephalopathy

Measurement of Serum, Liver, and Brain Cytokine Induction, Thiamine Levels, and Hepatopathology in Rats Exposed to a 4‐Day Alcohol Binge Protocol

Myoinositol as a Biomarker in Recurrent Glioblastoma Treated with Bevacizumab: A 1H-Magnetic Resonance Spectroscopy Study

Contact Info

Product

Resources

About