scholarly journals A novel roadmap connecting the 1H-MRS total choline resonance to all hallmarks of cancer following targeted therapy

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Egidio Iorio ◽  
Franca Podo ◽  
Martin O. Leach ◽  
Jason Koutcher ◽  
Francis G. Blankenberg ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cell Signalling ◽  
Imaging Biomarker ◽  
Resonance Spectroscopy ◽  
Membrane Turnover ◽  
1H Mrs ◽  
Cancer Hallmarks ◽  
Signalling Network ◽  
Total Membrane ◽  
Stress Signalling

AbstractThis review describes a cellular adaptive stress signalling roadmap connecting the 1H magnetic resonance spectroscopy (MRS) total choline peak at 3.2 ppm (tCho) to cancer response after targeted therapy (TT). Recent research on cell signalling, tCho metabolism, and TT of cancer has been retrospectively re-examined. Signalling research describes how the unfolded protein response (UPR), a major stress signalling network, transduces, regulates, and rewires the total membrane turnover in different cancer hallmarks after a TT stress. In particular, the UPR signalling maintains or increases total membrane turnover in all pro-survival hallmarks, whilst dramatically decreases turnover during apoptosis, a pro-death hallmark. Recent research depicts the TT-induced stress as a crucial event responsible for interrupting UPR pro-survival pathways, leading to an UPR-mediated cell death. The 1H-MRS tCho resonance represents the total mobile precursors and products during the enzymatic modification of phosphatidylcholine membrane abundance. The tCho profile represents a biomarker that noninvasively monitors TT-induced enzymatic changes in total membrane turnover in a wide variety of existing and new anticancer treatments targeting specific layers of the UPR signalling network. Our overview strongly suggests further evaluating and validating the 1H-MRS tCho peak as a powerful noninvasive imaging biomarker of cancer response in TT clinical trials.

Abstract 99: A Magnetic Resonance Spectroscopy [1H-MRS] Study of Peri-infarct Neuro-glial Interactions in Recovering Stroke Patients

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Ndaba Mazibuko ◽  
Ruth O'Gorman ◽  
Owen O’Daly ◽  
Fernando Zelaya ◽  
Steven Williams ◽  
...  
Keyword(s):  
Significant Rise ◽  
Adult Brain ◽  
Resonance Spectroscopy ◽  
Motor Impairments ◽  
Stroke Patients ◽  
Membrane Turnover ◽  
1H Mrs ◽  
Time Points ◽  
Positive Correlations ◽  
Cr Concentration

Background: The adult brain has the capacity to reorganize after acute stroke and the ability to follow neuroplastic processes can be useful in predicting and monitoring recovery after stroke. This study investigates the ability of 1H-MRS to measure metabolic events in the structurally intact peri-infarct region between 2-12 weeks after stroke and their relationship to motor recovery. Method: The study included 15 first-ever stroke patients aged 18-75 years and age/sex matched controls. Structural, perfusion and 1H-MRS imaging was undertaken to measure regional cerebral blood flow (rCBF), N-acetylaspartate (NAA), choline (Cho), myoinositol (mI), creatine (cr) and lactate in the ipsilesional and contralesional hemisphere of stroke patients at 2 weeks, 6±1 and 12±3 weeks after stroke onset. Simultaneous clinical assessments were undertaken to measure motor impairments using the Fugl-Meyer [F-M]) scale. Patients were compared with controls at all time-points and the relationships between metabolites and with motor outcome were assessed. Results: Stroke patients were aged 51.4 (SD 13.3) years and all improved significantly between 2 and 12 weeks. Ipsilesional rCBF was decreased (22.7 v 36.8 mL/100 g/min, p=0.0036) at 2 weeks but increased to normal values by 12 weeks. Cr concentration (energy balance) were decreased in parallel and increased to normal concentration by 12 weeks. Ipsilesional NAA (neuronal integrity) was similar to healthy controls at 2 weeks it decreased significantly by 6 weeks. Cho (membrane turnover) significantly higher compared with controls at all time points; mI (glial cells) did not differ at 2 weeks but increased significantly between 2 and 12 weeks and there was a significant rise in lactate (inflammation) concentration at 12 weeks. There were strong positive correlations of rCBF with NAA at 12 weeks (r=0.42, p <0.002), NAA at 2 and 12 weeks with FM scores at 12 weeks (r = 0.79, p= 0.004, r = 0.799, p = 0.006) and rCBF with change in F-M score between 2-12 weeks (r = 0.44, p=0.01). Conclusions: Ipsilesional CBF and metabolite estimation may be a sensitive tool to quantify vascular and neuro-glial interactions in the spared cortex after stroke that can be used to predict and monitor recovery.

scholarly journals Glutamate connectivity associations converge upon the salience network in schizophrenia and healthy controls

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert A. McCutcheon ◽  
Toby Pillinger ◽  
Maria Rogdaki ◽  
Juan Bustillo ◽  
Oliver D. Howes
Keyword(s):  
Functional Connectivity ◽  
Frontal Cortex ◽  
Network Connectivity ◽  
Resonance Spectroscopy ◽  
Salience Network ◽  
Healthy Controls ◽  
1H Mrs ◽  
Before And After ◽  
Functional Brain Networks ◽  
The Relationship

AbstractAlterations in cortical inter-areal functional connectivity, and aberrant glutamatergic signalling are implicated in the pathophysiology of schizophrenia but the relationship between the two is unclear. We used multimodal imaging to identify areas of convergence between the two systems. Two separate cohorts were examined, comprising 195 participants in total. All participants received resting state functional MRI to characterise functional brain networks and proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate concentrations in the frontal cortex. Study A investigated the relationship between frontal cortex glutamate concentrations and network connectivity in individuals with schizophrenia and healthy controls. Study B also used 1H-MRS, and scanned individuals with schizophrenia and healthy controls before and after a challenge with the glutamatergic modulator riluzole, to investigate the relationship between changes in glutamate concentrations and changes in network connectivity. In both studies the network based statistic was used to probe associations between glutamate and connectivity, and glutamate associated networks were then characterised in terms of their overlap with canonical functional networks. Study A involved 76 individuals with schizophrenia and 82 controls, and identified a functional network negatively associated with glutamate concentrations that was concentrated within the salience network (p < 0.05) and did not differ significantly between patients and controls (p > 0.85). Study B involved 19 individuals with schizophrenia and 17 controls and found that increases in glutamate concentrations induced by riluzole were linked to increases in connectivity localised to the salience network (p < 0.05), and the relationship did not differ between patients and controls (p > 0.4). Frontal cortex glutamate concentrations are associated with inter-areal functional connectivity of a network that localises to the salience network. Changes in network connectivity in response to glutamate modulation show an opposite effect compared to the relationship observed at baseline, which may complicate pharmacological attempts to simultaneously correct glutamatergic and connectivity aberrations.

scholarly journals Striatal glutamate and the conversion to psychosis: a prospective 1H-MRS imaging study

2012 ◽  
Vol 16 (2) ◽  
pp. 471-475 ◽  
Author(s):  
Camilo de la Fuente-Sandoval ◽  
Pablo León-Ortiz ◽  
Mariana Azcárraga ◽  
Rafael Favila ◽  
Sylvana Stephano ◽  
...  
Keyword(s):  
Proton Magnetic Resonance ◽  
Proton Magnetic Resonance Spectroscopy ◽  
Imaging Study ◽  
Psychotic Symptoms ◽  
Resonance Spectroscopy ◽  
Control Groups ◽  
1H Mrs ◽  
Ultra High Risk ◽  
And Control

Abstract Increased glutamate levels in the associative-striatum have been described in subjects at ultra-high risk for psychosis (UHR); nevertheless, it is unclear whether this abnormality predicts the conversion to psychosis. Nineteen subjects at UHR and 26 controls were studied using proton magnetic resonance spectroscopy. Subjects at UHR were clinically followed for 2 yr. Seven UHR subjects (37%) transitioned to a psychotic disorder and the remaining 12 did not exhibit psychotic symptoms at the most recent follow-up. The psychosis transition group had higher glutamate levels compared to both non-transition and control groups (p = 0.02 and p < 0.01, respectively; effect size 1.39). These pilot findings suggest that the conversion to psychosis is associated with increased glutamate levels in the associative-striatum.

scholarly journals 81 IN VIVO PROTON MAGNETIC RESONANCE SPECTROSCOPY (1H-MRS) IN CYSTIC LEUCOMALACIA OF INFANCY

1994 ◽  
Vol 36 (1) ◽  
pp. 16A-16A
Author(s):  
Floris Groenendaal ◽  
Paula Eken ◽  
Jeroen Van Der Grond ◽  
Karin Rademaker ◽  
Linda S De Vries
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Proton Magnetic Resonance ◽  
Proton Magnetic Resonance Spectroscopy ◽  
Resonance Spectroscopy ◽  
1H Mrs

scholarly journals Morphological and Metabolic Alteration of Cerebellum in Patients with Post-Stroke Depression

2016 ◽  
Vol 40 (3-4) ◽  
pp. 420-430 ◽  
Author(s):  
Ling Zhang ◽  
Rubo Sui ◽  
Lei Zhang ◽  
Zhuang Zhang
Keyword(s):  
Magnetic Resonance ◽  
Depression Scale ◽  
Resonance Spectroscopy ◽  
Hamilton Depression Scale ◽  
Stroke Patients ◽  
1H Mrs ◽  
Post Stroke ◽  
Cont Group ◽  
Post Stroke Depression ◽  
Norm Group

Background: To study morphological and metabolic changes of cerebellum with multimodality magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS), respective, to explore correlation between cerebellum alteration and severity of depression in patients with post-stroke depression. Methods: 60 subjects, including 40 stroke patients and 20 healthy volunteers were enrolled. Depression of stroke patients was tested by Self-rating Depression Scale (SDS) and Hamilton Depression Scale (HAMD), based on which stroke-patients were grouped into post-stroke depression (PSD group) and without post-stroke depression (CONT group). Results: Volume of cerebellum decreased in PSD group and CONT group compared with healthy volunteer (NORM) group. White matter of cerebellum in PSD group and CONT group was disrupted; such disruption was significantly in PSD group. In addition, there was correlation between cerebellum volume and FA and HDRS scores (P<00.01). The Cho/Cr and Cho/NAA ratios in cerebellum contralateral to stroke lesion in PSD were higher than those in NORM group (P<0.05). Cho/Cr and Cho/NAA ratios in contralateral cerebellum and ratio difference of Cho/Cr in bilateral cerebellum were positively correlated with HAMD scales (P<0.05). Conclusion: Morphologic and metabolic alterations are evident in patients with post-stroke depression, indicating possible involvement of cerebellum in post-stroke-depression occurrence.

scholarly journals Early metabolic changes measured by 1H MRS in healthy and dystrophic muscle after injury

2012 ◽  
Vol 113 (5) ◽  
pp. 808-816 ◽  
Author(s):  
Su Xu ◽  
Stephen J. P. Pratt ◽  
Espen E. Spangenburg ◽  
Richard M. Lovering
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Tibialis Anterior Muscle ◽  
Metabolic Changes ◽  
Mdx Mice ◽  
Resonance Spectroscopy ◽  
Dystrophic Muscle ◽  
1H Mrs ◽  
Skeletal Muscle Injury

Skeletal muscle injury is often assessed by clinical findings (history, pain, tenderness, strength loss), by imaging, or by invasive techniques. The purpose of this work was to determine if in vivo proton magnetic resonance spectroscopy (1H MRS) could reveal metabolic changes in murine skeletal muscle after contraction-induced injury. We compared findings in the tibialis anterior muscle from both healthy wild-type (WT) muscles (C57BL/10 mice) and dystrophic ( mdx mice) muscles (an animal model for human Duchenne muscular dystrophy) before and after contraction-induced injury. A mild in vivo eccentric injury protocol was used due to the high susceptibility of mdx muscles to injury. As expected, mdx mice sustained a greater loss of force (81%) after injury compared with WT (42%). In the uninjured muscles, choline (Cho) levels were 47% lower in the mdx muscles compared with WT muscles. In mdx mice, taurine levels decreased 17%, and Cho levels increased 25% in injured muscles compared with uninjured mdx muscles. Intramyocellular lipids and total muscle lipid levels increased significantly after injury but only in WT. The increase in lipid was confirmed using a permeable lipophilic fluorescence dye. In summary, loss of torque after injury was associated with alterations in muscle metabolite levels that may contribute to the overall injury response in mdx mice. These results show that it is possible to obtain meaningful in vivo 1H MRS regarding skeletal muscle injury.

BIOM-14. METABOLIC BIOMARKERS OF TERT-TARGETED THERAPY FOR HUMAN GLIOBLASTOMA DETECTED BY MAGNETIC RESONANCE SPECTROSCOPY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi13-vi13
Author(s):  
Noriaki Minami ◽  
Donghyun Hong ◽  
Nicholas Stevers ◽  
Georgios Batsios ◽  
Anne Marie Gillespie ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
1H Mrs ◽  
Significant Drop ◽  
Knock Down ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Metabolic Data ◽  
Metabolic Biomarkers ◽  
Promoter Mutations ◽  
Tert Expression

Abstract BACKGROUND TERT promoter mutations that result in TERT expression are observed in over 80% of GBM. Moreover, the upstream transcription factor GABPB1 was recently identified as an ideal therapeutic target for tumors with TERT promoter mutations. In that context, non-invasive reliable biomarkers that can help detect TERT expression are needed. The aim of this research was to assess the value of MRS-detectable metabolic changes as biomarkers of TERT expression and TERT-targeted therapy in GBM. METHODS Genetically engineered GBM cells (NHARas/TERT) treated with TERT siRNA were compared to siCtrl-treated cells, and stable TERT and GABPB1 knock down GBM cells (U251, GBM1) were compared to shCtrl. 1H-MRS and 13C-MRS metabolic data was acquired from cell extracts using a Bruker 500MHz scanner. Hyperpolarized MRS studies of live cells used a HyperSense DNP polarizer and data was acquired using a Varian 500MHz scanner. Spectra were analyzed using Mnova and Matlab software. Multivariate data analysis was performed using SIMCA software. RESULTS Unbiased PCA analysis of 1H-MRS metabolic data showed separation of TERT or GABPB1 knock down and control cells. VIP predictive scores revealed that lactate and GSH were the top altered metabolites with a significant drop observed in both metabolites in every model following TERT silencing. Consistent with the reduction in GSH, spectrophotometric assays showed a significant drop in NADPH and NADH. 2-13C glucose flux analysis revealed that both glycolysis and PPP-related metabolites were reduced in TERT knock down cells. Hyperpolarized [1-13C]-pyruvate flux to lactate was also reduced, confirming that the glycolytic pathway was altered following TERT knock down. CONCLUSION 1H MRS-detectable lactate and GSH, combined with hyperpolarized 13C MRS-detectable metabolic fluxes, could serve as metabolic biomarkers of TERT-targeted therapy for human GBM with TERT promoter mutations. These biomarkers could be translated to the clinical, improve the monitoring of GBM patients and advance precision medicine.

scholarly journals Comparison of human brain metabolite levels using 1H MRS at 1.5T and 3.0T

2013 ◽  
Vol 7 (2) ◽  
pp. 216-220 ◽  
Author(s):  
Fernando Fernandes Paiva ◽  
Maria Concepcion Garcia Otaduy ◽  
Ricardo de Oliveira-Souza ◽  
Jorge Moll ◽  
Ivanei Edson Bramati ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Field Strength ◽  
Human Brain ◽  
Psychiatric Disorders ◽  
Posterior Cingulate Cortex ◽  
Resonance Spectroscopy ◽  
1H Mrs ◽  
Metabolite Concentrations ◽  
Expected Benefits ◽  
The Magnetic Field

ABSTRACT Proton magnetic resonance spectroscopy (MRS) of the human brain has proven to be a useful technique in several neurological and psychiatric disorders and benefits from higher field scanners as signal intensity and spectral resolution are proportional to the magnetic field strength. Objective: To investigate the effects of the magnetic field on the measurement of brain metabolites in a typical routine clinical setting. Methods: Single voxel spectra were acquired from the posterior cingulate cortex in 26 healthy subjects. Each subject was scanned consecutively at 1.5T and 3.0T in a randomly distributed order. Results: SNR and peak width improvements were observed at higher fields. However, SNR improvement was lower than the theoretical two-fold improvement. Other than the values obtained for creatine (Cre) and myo-Inositol (mI), which were both higher at 3.0T, all metabolite concentrations obtained were roughly the same at both field strengths. All the metabolite concentrations were estimated with a Cramer Rao lower bounds (CRLB) lower than 15% of the calculated concentrations. Conclusions: Even though the present study supports the expected benefits of higher field strength for MRS, there are several factors that can lead to different quantitative results when comparing 1.5T to 3.0T MRS. Future comparative studies are necessary to refine the metabolite thresholds for early detection and quantification of distinct neurological and psychiatric disorders using 3.0T MRS.

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