NIMG-44. PROGNOSTIC VALUE OF PH- AND OXYGEN-SENSITIVE MRI IN GLIOMA PATIENTS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi138-vi139
Author(s):  
Yao Jingwen ◽  
Akifumi Hagiwara ◽  
Talia Oughourlian ◽  
Chencai Wang ◽  
Catalina Raymond ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Cox Regression ◽  
Pulse Sequence ◽  
Chemical Exchange ◽  
Chemical Exchange Saturation Transfer ◽  
Magnetization Transfer Ratio ◽  
Who Grade ◽  
Vast Number ◽  
Tumor Acidity ◽  
Oxygen Sensitive

Abstract Hypoxia and tissue acidosis are two key features of the glioma microenvironment, both associated with a more aggressive phenotype through promotion of invasion, angiogenesis, and resistance to a vast number of therapies. In the current study, we demonstrate that higher levels of acidity and hypoxia in glioma are associated with worse prognosis by using simultaneous pH- and oxygen-sensitive amine chemical exchange saturation transfer spin-and-gradient echo echo-planar imaging (CEST-SAGE-EPI). A total of 159 histologically confirmed adult glioma patients (WHO grade II: N = 42; grade III: N = 38; grade IV, N = 79) were retrospectively evaluated. All patients were scanned with a custom amine CEST-SAGE-EPI MRI pulse sequence at 3T. Magnetization transfer ratio asymmetry (MTRasym) at 3ppm was used as a measure of relative acidity, R2’ was used as a surrogate of hypoxia, and their product MTRasym×R2' was used to quantify the degree of both acidity and hypoxia. Cox regression was performed to evaluate prognostic factors for OS and PFS. Univariate results suggested higher hypoxia, R2' (HR = 1.44, p = 0.0002), and higher combined measure of acidity and hypoxia, MTRasym×R2' (HR = 1.14, p = 0.0008), were associated with a shorter OS. When considering age, treatment status, and IDH mutation status as covariates, R2' and MTRasym×R2' remained significantly associated with patient OS (R2': HR = 1.27, p = 0.045; MTRasym×R2': HR = 1.17, p = 0.002). Within the treatment naïve patients, tumor acidity MTRasym, was also associated with OS (HR = 3.72, p = 0.003). R2' and MTRasym×R2' were significantly associated with PFS, both using univariate (R2': p < 0.0001; MTRasym×R2': p < 0.0001) and multivariate analyses including clinical factors (R2': p = 0.010; MTRasym×R2': p < 0.0001). In summary, tumor acidity and hypoxia measured using pH- and oxygen-sensitive metabolic MRI are significant prognostic factors in glioma.

scholarly journals Analysis of Prognostic Factors of World Health Organization Grade Ⅲ Meningiomas

2020 ◽  
Vol 10 ◽  
Author(s):  
Weidong Tian ◽  
Jingdian Liu ◽  
Kai Zhao ◽  
Junwen Wang ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
World Health ◽  
Low Grade ◽  
Ki 67 ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

ObjectiveWHO grade III meningiomas are highly aggressive and lethal. However, there is a paucity of clinical information because of a low incidence rate, and little is known for prognostic factors. The aim of this work is to analyze clinical characteristics and prognosis in patients diagnosed as WHO grade III meningiomas.Methods36 patients with WHO grade III meningiomas were enrolled in this study. Data on gender, age, clinical presentation, preoperative Karnofsky Performance Status (KPS), histopathologic features, tumor size, location, radiologic findings, postoperative radiotherapy (RT), surgical treatment, and prognosis were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were conducted by the Cox regression model.ResultsMedian PFS is 20 months and median OS is 36 months in 36 patients with WHO grade III meningiomas. Patients with secondary tumors which transformed from low grade meningomas had lower PFS (p=0.0014) compared with primary group. Multivariate analysis revealed that tumors location (PFS, p=0.016; OS, p=0.013), Ki-67 index (PFS, p=0.004; OS, p<0.001) and postoperative radiotherapy (PFS, p=0.006; OS, p<0.001) were associated with prognosis.ConclusionWHO grade III meningiomas which progressed from low grade meningiomas were more prone to have recurrences or progression. Tumors location and Ki-67 index can be employed to predict patient outcomes. Adjuvant radiotherapy after surgery can significantly improve patient prognosis.

scholarly journals Neutrophil Extracellular Traps and Macrophage Extracellular Traps Predict Postoperative Recurrence in Resectable Nonfunctional Pancreatic Neuroendocrine Tumors

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuai-Shuai Xu ◽  
Hao Li ◽  
Tian-Jiao Li ◽  
Shuo Li ◽  
Huan-Yu Xia ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Information Criteria ◽  
Rank Test ◽  
Calibration Plot ◽  
Pancreatic Neuroendocrine Tumors ◽  
Regression Analyses ◽  
Who Grade ◽  
Extracellular Traps

BackgroundExtracellular traps (ETs) and tumor-infiltrating immune cells can contribute to disease progression. The clinical significance of tumor-infiltrating neutrophils and macrophages and related extracellular traps in pancreatic neuroendocrine tumors (pNETs) has not been fully elucidated. This study aimed to explore the prognostic value of tumor infiltration and ET formation by neutrophils and macrophages in pNETs.MethodsA total of 135 patients with radical resection of nonfunctional pNETs were analyzed retrospectively. Immunohistochemistry and immunofluorescence were utilized to stain tumor tissue sections. The recurrence-free survival (RFS) of subgroups determined by Kaplan-Meier analysis was compared with the log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram was established to predict 3-year RFS.ResultsPatients with high tumor-infiltrating neutrophils or macrophages or positive expression of neutrophils ETs or macrophage ETs displayed worse RFS (all p<0.05). Moreover, univariate and multivariate Cox regression analyses showed that neutrophil and macrophage infiltration and ETs were independent prognostic factors for RFS (all p<0.05). A combined parameter including WHO grade, TNM stage, tumor-infiltrating neutrophils and macrophages, and neutrophil and macrophage ETs had the highest C-index (0.866) and lowest Akaike information criteria (326.557). The calibration plot of nomogram composed of the combined parameter exhibited excellent prognostic values for 3-year RFS.ConclusionsInfiltration and ETs by neutrophils and macrophages can be used as biological indicators of patient prognosis, suggesting the treatment potential for targeting those in nonfunctional pNETs.

scholarly journals Incidence, Risk Factors, and Prognosis of Meningiomas With Distant Metastases at Presentation

2021 ◽  
Author(s):  
Huy Gia Vuong ◽  
Tam N.M. Ngo ◽  
Ian F. Dunn
Keyword(s):  
Prognostic Factors ◽  
Cox Regression ◽  
Rare Event ◽  
Distant Metastases ◽  
Extent Of Resection ◽  
Male Gender ◽  
Standards Of Care ◽  
Rank Test ◽  
Large Tumor ◽  
Who Grade

Abstract IntroductionDistant metastases (DM) at presentation in meningiomas is a very rare event, and the incidence and factors predicting this are uncertain. This population-based study also aimed to investigate the prognostic implication of DM at presentation and clinical parameters to prognosticate the overall survival (OS) of meningiomas presenting with DM (M1).MethodsWe accessed the Surveillance, Epidemiology, and End Results program to search for patients who were diagnosed with meningioma between 2004-2016. The log-rank test was used to compare Kaplan-Meier survival curves and multivariate Cox regression model was utilized to evaluate the prognostic parameters of meningiomas with DM at presentation.ResultsThe incidence of DM at presentation among all meningiomas was 0.18%. Clinical variables associated with this event were male gender, large tumor size, and WHO grade III. The presence of DM at diagnosis conferred a shorter survival in comparison to those without DM (HR = 2.015; 95% CI = 1.600-2.536). Older patient age, male gender, malignant histology, and the lesser extent of resection were independent prognostic factors that could negatively impact OS of M1 meningiomas. Radiotherapy and chemotherapy were not associated with an improved outcome for these patients.ConclusionOur study highlighted the clinical and prognostic factors of M1 meningiomas. These data suggest that a greater extent of resection is associated with increased OS across a nationwide analysis and emphasize the need to establish the standards of care in these patients.

scholarly journals 3D APT and NOE CEST-MRI of healthy volunteers and patients with non-enhancing glioma at 3 T

2022 ◽  
Author(s):  
Yulun Wu ◽  
Tobias Charles Wood ◽  
Fatemeh Arzanforoosh ◽  
Juan Antonio Hernandez-Tamames ◽  
Gareth John Barker ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Tumor Heterogeneity ◽  
Chemical Exchange ◽  
Magnetization Transfer ◽  
Chemical Exchange Saturation Transfer ◽  
Amide Proton ◽  
Magnetization Transfer Ratio ◽  
Normal Appearing White Matter ◽  
Saturation Power ◽  
Cest Mri

Abstract Objective Clinical application of chemical exchange saturation transfer (CEST) can be performed with investigation of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) effects. Here, we investigated APT- and NOE-weighted imaging based on advanced CEST metrics to map tumor heterogeneity of non-enhancing glioma at 3 T. Materials and methods APT- and NOE-weighted maps based on Lorentzian difference (LD) and inverse magnetization transfer ratio (MTRREX) were acquired with a 3D snapshot CEST acquisition at 3 T. Saturation power was investigated first by varying B1 (0.5–2 µT) in 5 healthy volunteers then by applying B1 of 0.5 and 1.5 µT in 10 patients with non-enhancing glioma. Tissue contrast (TC) and contrast-to-noise ratios (CNR) were calculated between glioma and normal appearing white matter (NAWM) and grey matter, in APT- and NOE-weighted images. Volume percentages of the tumor showing hypo/hyperintensity (VPhypo/hyper,CEST) in APT/NOE-weighted images were calculated for each patient. Results LD APT resulting from using a B1 of 1.5 µT was found to provide significant positive TCtumor,NAWM and MTRREX NOE (B1 of 1.5 µT) provided significant negative TCtumor,NAWM in tissue differentiation. MTRREX-based NOE imaging under 1.5 µT provided significantly larger VPhypo,CEST than MTRREX APT under 1.5 µT. Conclusion This work showed that with a rapid CEST acquisition using a B1 saturation power of 1.5 µT and covering the whole tumor, analysis of both LD APT and MTRREX NOE allows for observing tumor heterogeneity, which will be beneficial in future studies using CEST-MRI to improve imaging diagnostics for non-enhancing glioma.

Chemical exchange saturation transfer for detection of antiretroviral drugs in brain tissue

2021 ◽  
Author(s):  
Aditya N. Bade ◽  
Howard E. Gendelman ◽  
JoEllyn McMillan ◽  
Yutong Liu
Keyword(s):  
Chemical Exchange ◽  
Magnetization Transfer ◽  
Antiretroviral Drugs ◽  
Chemical Exchange Saturation Transfer ◽  
Magnetization Transfer Ratio ◽  
Saturation Transfer ◽  
Viral Reservoirs ◽  
Drug Concentrations ◽  
Imaging Results ◽  
Magnetic Resonance Imaging Mri

AbstractHuman immunodeficiency virus type-1 (HIV-1) antiretroviral drug (ARV) theranostics facilitates biodistribution and efficacy of therapies designed to target viral reservoirs. To this end, we have now deployed intrinsic drug chemical exchange saturation transfer (CEST) contrast to detect ARV distribution within the central nervous system (CNS).MethodsCEST effects for lamivudine (3TC) and emtricitabine (FTC) were measured by asymmetric magnetization transfer ratio analyses in solutions. CEST magnetic resonance imaging (MRI) was performed on 3TC-treated mice with analysis made by Lorentzian fitting.ResultsCEST effects of 3TC and FTC hydroxyl and amino protons linearly correlated to drug concentrations. 3TC was successfully detected in brain sub-regions by MRI. The imaging results were validated by measurements of CNS drug concentrations.ConclusionCEST contrasts can be used to detect ARVs using MRI. Such detection can be used to assess spatial-temporal drug biodistribution. This is most notable within the CNS where drug biodistribution may be more limited with the final goal of better understanding ARV-associated efficacy and potential toxicity.

scholarly journals Saturation transfer MRI is sensitive to neurochemical changes in the rat brain due to chronic unpredictable mild stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Pankowska ◽  
Agata Chudzik ◽  
Tymoteusz Słowik ◽  
Artur Łazorczyk ◽  
Katarzyna Kochalska ◽  
...  
Keyword(s):  
Chemical Exchange ◽  
Nuclear Overhauser Effect ◽  
Magnetization Transfer ◽  
Brain Regions ◽  
Chemical Exchange Saturation Transfer ◽  
Magnetization Transfer Ratio ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Saturation Transfer ◽  
Neurochemical Changes

AbstractChemical exchange saturation transfer (CEST) MRI was performed for the evaluation of cerebral metabolic changes in a rat model of depressive-like disease induced by chronic unpredictable mild stress (CUMS). CEST Z-spectra were acquired on a 7 T MRI with two saturation B1 amplitudes (0.5 and 0.75 µT) to measure the magnetization transfer ratio (MTR), CEST and relayed nuclear Overhauser effect (rNOE). Cerebral cortex and hippocampus were examined in two groups of animals: healthy control (n = 10) and stressed (n = 14), the latter of which was exposed to eight weeks of the CUMS protocol. The stressed group Z-spectrum parameters, primarily MTRs, were significantly lower than in controls, at all selected frequency offsets (3.5, 3.0, 2.0, − 3.2, − 3.6 ppm) in the cortex (the largest difference of ~ 3.5% at − 3.6 ppm, p = 0.0005) and the hippocampus (MTRs measured with a B1 = 0.5 µT). The hippocampal rNOE contributions decreased significantly in the stressed brains. Glutamate concentration (assessed using ELISA) and MTR at 3 ppm correlated positively in both brain regions. GABA concentration also correlated positively with CEST contributions in both cerebral areas, while such correlation with MTR was positive in hippocampus, and nonsignificant in cortex. Results indicate that CEST is sensitive to neurometabolic changes following chronic stress exposure.

scholarly journals Preliminary application of 3.0T magnetic resonance chemical exchange saturation transfer imaging in brain metastasis of lung cancer

2019 ◽  
Author(s):  
Yonggui Yang ◽  
Xiaobo QU ◽  
Yihui HUANG ◽  
Afsar Khan ◽  
Gen Yan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Chemical Exchange ◽  
Magnetization Transfer ◽  
Metastatic Tumor ◽  
Chemical Exchange Saturation Transfer ◽  
Magnetization Transfer Ratio ◽  
Saturation Transfer ◽  
Tumor Group ◽  
Significant Difference

Abstract Background: Lung cancer brain metastases are very common and one of the common causes of treatment failure. We aimed to examine the clinical use of chemical exchange saturation transfer(CEST) technology in the evaluation of brain metastases for lung cancer diagnosis and prognosis. Methods: We included26 cases of lung cancer brain metastases, 15 cases of gliomas, and 20 cases with normal tests. The magnetization transfer ratio (MTR;3.5ppm) image from the GRE-EPI-CEST sequence was analyzed using the ASSET technique and APT technology. The MTR values were measured in the lesion-parenchymal, edema, and non-focus regions, and the MTR image was compared with the conventional MRI. ANOVA and t-test were used for statistical analysis. Results: The lesion-parenchymal, edema, and non-focus areas in the metastatic-tumor-group were red-yellow, yellow-green, and green-blue, and the MTR values were 3.29±1.14%,1.28±0.36%,and 1.26±0.31%, respectively. However, in the glioma-group, the corresponding areas were red, red-yellow, and green-blue, and the MTR values were 6.29±1.58%, 2.87±0.65%, and 1.03±0.30%, respectively. The MTR values of the corresponding areas in the normal-group were 1.07±0.22%,1.04±0.23%, and 1.06±0.24%, respectively. Traditional MR images are in black-white contrast and no metabolic information is displayed. The MTRvalues of the three regions were significantly different among the three groups. The values were also significantly different between the parenchymal and edema areas in the metastatic-tumor-group. There were significant differences in the MTR values between the non-lesion and edema regions, but there was no significant difference between the edema and non-focus areas. In the glioma-group, there were significant differences in the MTR values between the parenchymal and edema areas, between the parenchymal and non-focus areas, and between the edema and non-focus areas. Conclusions: CEST reflects the protein metabolism; therefore, early diagnosis of brain metastases and assessment of the prognosis can be achieved using molecular imaging.

scholarly journals Temporal Changes in In Vivo Glutamate Signal during Demyelination and Remyelination in the Corpus Callosum: A Glutamate-Weighted Chemical Exchange Saturation Transfer Imaging Study

2020 ◽  
Vol 21 (24) ◽  
pp. 9468
Author(s):  
Do-Wan Lee ◽  
Hwon Heo ◽  
Chul-Woong Woo ◽  
Dong-Cheol Woo ◽  
Jeong-Kon Kim ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Chemical Exchange ◽  
Magnetization Transfer ◽  
Imaging Study ◽  
Chemical Exchange Saturation Transfer ◽  
Cerebral White Matter ◽  
Magnetization Transfer Ratio ◽  
Saturation Transfer ◽  
Clinical Magnetic Resonance Imaging

Background: Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool that can be used to detect changes in glutamate levels in vivo and could also be helpful in the diagnosis of brain myelin changes. We investigated glutamate level changes in the cerebral white matter of a rat model of cuprizone-administered demyelination and remyelination using GluCEST. Method: We used a 7 T pre-clinical magnetic resonance imaging (MRI) system. The rats were divided into the normal control (CTRL), cuprizone-administered demyelination (CPZDM), and remyelination (CPZRM) groups. GluCEST data were analyzed using the conventional magnetization transfer ratio asymmetry in the corpus callosum. Immunohistochemistry and transmission electron microscopy analyses were also performed to investigate the myelinated axon changes in each group. Results: The quantified GluCEST signals differed significantly between the CPZDM and CTRL groups (−7.25 ± 1.42% vs. −2.84 ± 1.30%; p = 0.001). The increased GluCEST signals in the CPZDM group decreased after remyelination (−6.52 ± 1.95% in CPZRM) to levels that did not differ significantly from those in the CTRL group (p = 0.734). Conclusion: The apparent temporal signal changes in GluCEST imaging during demyelination and remyelination demonstrated the potential usefulness of GluCEST imaging as a tool to monitor the myelination process.

NIMG-41. PH-WEIGHTED MOLECULAR MRI AS AN EARLY BIOMARKER OF METABOLIC RESPONSE TO IDH INHIBITION IN IDH MUTANT GLIOMAS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi138-vi138
Author(s):  
Benjamin Ellingson ◽  
Yao Jingwen ◽  
Akifumi Hagiwara ◽  
David Nathanson ◽  
Talia Oughourlian ◽  
...  
Keyword(s):  
Metabolic Response ◽  
Chemical Exchange ◽  
Phase 1 ◽  
Chemical Exchange Saturation Transfer ◽  
Flux Analysis ◽  
Low Grade ◽  
Wild Type ◽  
Molecular Mri ◽  
Glycolytic Activity ◽  
Tumor Acidity

Abstract The current study tested the hypotheses that (1) pH-weighted MRI measurements of tumor acidity reflect glycolytic activity in human gliomas, (2) that tumor acidity, and thus glycolytic activity, differs between human IDH mutant (mIDH) and wild type gliomas, and (3) that an increase in tumor acidity, suggestive of increased glycolytic activity, occurs after inhibition of mutant IDH enzyme activity and reduction in 2HG, an oncometabolite. To test these hypotheses, we employed a custom pH-weighted amine chemical exchange saturation transfer echoplanar (CEST-EPI) technique in 152 patients with IDH mutant or wildtype glioma prior to surgery and 11 patients before and after treatment with AG120 or AG881 enrolled at our institution in a phase 1 perioperative study in patients with recurrent, non-enhancing, IDH mutant low-grade gliomas (NCT03343197). Results from image-guided biopsies in more than 100 patients demonstrated a significant correlation between MTRasym at 3ppm, a measure of tumor acidity from pH-weighted amine CEST-EPI, and expression of key glycolytic proteins including GLUT3 (R2=0.2188,P=0.0105), HK2 (R2=0.1788,P=0.0314), LDHA (R2=0.1111,P=0.0071), and MCT1 (R2=0.1228,P=0.0039) as well as ex vivo extracellular flux analysis estimates of ATP consumption from glycolysis (R2=0.6684,P=0.0021). Data suggests a significantly lower acidity (MTRasym@3ppm) within non-enhancing tumor in IDH mutant gliomas when compared to IDH wild type gliomas (P< 0.0001). Patients in a phase 1 perioperative study showed a shift toward higher tumor acidity (i.e. higher glycolytic activity) following inhibition of IDH based on 2HG suppression in resected tumors, but at levels below that of IDH wild type gliomas. Levels of 2HG within the tumor after IDH inhibition were inversely correlated with post-treatment tumor acidity (R2=0.6342, P=0.0180). Overall, results suggest mIDH gliomas have low levels of glycolytic activity, and successful inhibition of the mutant IDH enzyme results in reduction in 2HG and a measurable metabolic shift toward elevated glycolysis as evidenced using pH-weighted molecular MRI.

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