scholarly journals NI-12 The ratio of T1-Weighted to T2-Weighted Signal Intensity and IDH mutation in glioma

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi20-vi20
Author(s):  
Takahiro Sanada ◽  
Shota Yamamoto ◽  
Hirotaka Sato ◽  
Mio Sakai ◽  
Masato Saito ◽  
...  
Keyword(s):  
Validation Cohort ◽  
Region Of Interest ◽  
University Hospital ◽  
Lower Grade ◽  
Idh Mutation ◽  
Mutation Status ◽  
Weighted Image ◽  
Clinically Significant ◽  
Tcga Dataset ◽  
T2 Weighted Images

Abstract Introduction: Prediction of IDH mutation status for Lower-grade glioma (LrGG) is clinically significant. The purpose of this study is to test the hypothesis that the T1-weighted image/T2-weighted image ratio (rT1/T2), an imaging surrogate developed for myelin integrity, is a useful MRI biomarker for predicting the IDH mutation status of LrGG. Methods: Twenty-five LrGG patients (IDHwt: 8, IDHmt: 17) at Asahikawa Medical University Hospital (AMUH) were used as an exploratory cohort. Twenty-nine LrGG patients (IDHwt: 13, IDHmt: 16) from Osaka International Cancer Institute (OICI) and 103 patients from the Cancer Imaging Archive (TCIA) / Cancer Genome Atlas (TCGA) dataset (IDHwt: 19, IDHmt: 84) were used as validation cohorts. rT1/T2 images were calculated from T1- and T2-weighted images using a recommended signal correction. The region-of-interest was defined on T2-weighted images, and the relationship between the mean rT1/T2 (mrT1/T2) and the IDH mutation status was investigated. Results: The mrT1/T2 was able to significantly predict the IDH mutation status for the AMUH exploratory cohort (AUC = 0.75, p = 0.048). The ideal cut-off for detecting mutant IDH was mrT1/T2 < 0.666 ~ 0.677, with a sensitivity of 58.8% and a specificity of 87.5%. This result was further validated by the OICI validation cohort (AUC = 0.75, p = 0.023) with a sensitivity of 56.3% and a specificity of 69.2%. On the other hand, the sensitivity was 42.9% and the specificity was 68.4 % for the TCIA validation cohort (AUC = 0.63, p = 0.068). Conclusion: Our results supported the hypothesis that mrT1/T2 could be a useful image surrogate to predict the IDH mutation status of LrGG using two domestic cohorts. The decline of the accuracy for the TCIA cohort should be further investigated.

scholarly journals IDH mutation status is associated with distinct vascular gene expression signatures in lower-grade gliomas

2018 ◽  
Vol 20 (11) ◽  
pp. 1505-1516 ◽  
Author(s):  
Lei Zhang ◽  
Liqun He ◽  
Roberta Lugano ◽  
Kenney Roodakker ◽  
Michael Bergqvist ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Lower Grade ◽  
Idh Mutation ◽  
Wild Type ◽  
Who Grade ◽  
Mutation Status ◽  
Grade Ii ◽  
Grade Ii Glioma

Abstract Background Vascular gene expression patterns in lower-grade gliomas (LGGs; diffuse World Health Organization [WHO] grades II–III gliomas) have not been thoroughly investigated. The aim of this study was to molecularly characterize LGG vessels and determine if tumor isocitrate dehydrogenase (IDH) mutation status affects vascular phenotype. Methods Gene expression was analyzed using an in-house dataset derived from microdissected vessels and total tumor samples from human glioma in combination with expression data from 289 LGG samples available in the database of The Cancer Genome Atlas. Vascular protein expression was examined by immunohistochemistry in human brain tumor tissue microarrays (TMAs) representing WHO grades II–IV gliomas and nonmalignant brain samples. Regulation of gene expression was examined in primary endothelial cells in vitro. Results Gene expression analysis of WHO grade II glioma indicated an intermediate stage of vascular abnormality, less severe than that of glioblastoma vessels but distinct from normal vessels. Enhanced expression of laminin subunit alpha 4 (LAMA4) and angiopoietin 2 (ANGPT2) in WHO grade II glioma was confirmed by staining of human TMAs. IDH wild-type LGGs displayed a specific angiogenic gene expression signature, including upregulation of ANGPT2 and serpin family H (SERPINH1), connected to enhanced endothelial cell migration and matrix remodeling. Transcription factor analysis indicated increased transforming growth factor beta (TGFβ) and hypoxia signaling in IDH wild-type LGGs. A subset of genes specifically induced in IDH wild-type LGG vessels was upregulated by stimulation of endothelial cells with TGFβ2, vascular endothelial growth factor, or cobalt chloride in vitro. Conclusion IDH wild-type LGG vessels are molecularly distinct from the vasculature of IDH-mutated LGGs. TGFβ and hypoxia-related signaling pathways may be potential targets for anti-angiogenic therapy of IDH wild-type LGG.

NIMG-53. RATIO OF T1-WEIGHTED TO T2-WEIGHTED SIGNAL INTENSITY AND IDH MUTATION IN GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi141-vi141
Author(s):  
Manabu Kinoshita ◽  
Masato Uchikoshi ◽  
Koji Takano ◽  
Mio Sakai ◽  
Hideyuki Arita ◽  
...  
Keyword(s):  
Relaxation Time ◽  
Signal Intensity ◽  
Surrogate Marker ◽  
Radiological Feature ◽  
Lower Grade ◽  
Idh Mutation ◽  
T2 Relaxation Time ◽  
T2 Relaxation ◽  
Mutation Status ◽  
T1 And T2

Abstract INTRODUCTION Identifying IDH mutation status before treatment is essential for Lower-grade glioma (LrGG) treatment. We have previously revealed that IDH mutated LrGG consists of tumor tissues with significantly longer T1 and T2 relaxation time and is a useful radiological feature to identify IDH mutation status. The ratio of T1-weighted to T2-weighted signal intensity (rT1/T2) is a way to retrieve semi-quantitative relaxation time information of the tissue bypassing the need to perform relaxometry. This investigation aimed to elucidate the correlation between rT1/T2 and T1-, T2-relaxation time (-relax) in glioma tissue and to explore the possibility of rT1/T2 as a radiological surrogate marker to identify IDH mutation status in LrGG. MATERIALS AND METHODS We analyzed 8 LrGGs (IDHwt:4, IDHmt:2, IDHmt&1p19q-CODEL:2) in which relaxometry was performed. rT1/T2 maps were reconstructed as described in previous literature. Regions-of-interest were designed based on T2WI and FLAIR. The correlations between rT1/T2 and T1- and T2-relax were analyzed. Furthermore, We also investigated the correlation of IDH mutation status and rT1/T2. RESULTS 106,488 voxels were analyzed. The correlation between rT1/T2 and T1- and T2-relax were rT1/T2=1.6e-0.0003T1-relax and rT1/T2=1.2e-0.002T2-relax (R=0.77 and 0.70). rT1/T2 of IDH-wildtype tumor was significantly higher than that of IDH-mutant tumor (1.0 vs. 0.75, p< 0.0001). Voxel-wise analysis of rT1/T2 map was able to discriminate IDH-wildtype tumor from the mutant tumor with an AUC of 0.82. CONCLUSIONS rT1/T2, which can be calculated from MRI acquired during routine clinical practice, is a promising radiological surrogate marker to identify IDH mutation status in LrGG.

scholarly journals P04.11 Voxelwise correlation between vascular MRI parameters obtained with ASL and DSC is decreased in IDH-wt non-enhancing glioma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii31-iii31
Author(s):  
E A H Warnert ◽  
F Incekara ◽  
A J P E Vincent ◽  
J W Schouten ◽  
M J van den Bent ◽  
...  
Keyword(s):  
Cerebral Blood Volume ◽  
Correlation Coefficients ◽  
Region Of Interest ◽  
Dynamic Susceptibility ◽  
Idh Mutation ◽  
Dynamic Susceptibility Contrast ◽  
Mutation Status ◽  
Susceptibility Contrast ◽  
Perfusion Measurements ◽  
Future Work

Abstract BACKGROUND Comparative studies of dynamic susceptibility contrast (DSC) based measurement of cerebral blood volume (CBV) or cerebral blood flow (CBF) and arterial spin labelling (ASL) based measurement of CBF have previously shown good correlation of these parameters in human glioma. However, these studies were mostly done before inclusion of the mutation status of the isocitrate dehydrogenase (IDH) encoding gene in brain tumour classification. In light of the call for gadolinium-free imaging, here we investigate the effect of IDH-mutation status on the correlation between ASL and DSC-based perfusion measurements in non-enhancing glioma. MATERIAL AND METHODS Twenty-two patients with non-enhancing glioma and confirmed IDH-mutation status (next generation sequencing, 6 IDH-wildtype and 16 IDH-mutated) underwent 3T MRI scanning (GE, Milwaukee, WI, USA). Image acquisition included a 3D spiral pseudocontinuous ASL with time-encoded labelling (7 effective label delays from 0.8 to 2 s, reconstruction matrix 128x128x42, resolution 1.9x1.9x3.5 mm3), and 2D DSC imaging (122 TRs, TR/TE 1500m/18.6ms, 15 slices, voxel size: 1.88x1.88x4 mm3) in which a bolus of 7.5ml of gadolinium-based contrast agent (Gadovist, Bayer, Leverkussen, GE) was injected. A pre-load bolus of equal size was given 5 minutes prior to DSC imaging. DSC and ASL images were motion corrected and linearly registered to high resolution FLAIR images (FSL, version 5.0.9, Oxford, UK). DSC-relative CBV (rCBV), DSC-relative CBF (rCBF), and ASL-CBF maps were calculated via previously described methods. The glioma region of interest (ROI) was determined via manual segmentation on the FLAIR images. Voxel-wise Pearson’s linear correlation coefficients (ρ) within this ROI were calculated between ASL-CBF and DSC-rCBV, and between ASL-CBF and DSC-rCBF. RESULTS Normalised histograms indicate that IDH-wt glioma has higher values for ASL-CBF, DSC-rCBV, and DSC-rCBF than IDH-mutated glioma. IDH-wildtype glioma has a significantly lower ρ ASL-CBF vs DSC-rCBV and ρ ASL-CBF vs DSC-rCBF than IDH-mutated glioma (two-sample t-tests p < 0.05). CONCLUSION IDH-mutation status of non-enhancing glioma potentially affects the correlation between ASL-CBF and DSC-rCBF/rCBV and should be taken into account when moving towards ASL-only imaging. The decreased correlation between ASL and DSC-based vascular parameters in IDH-wt gliomas may be due to more aggressive vasculature in subtypes of IDH-wt tumours. Future work includes expansion of the current patient cohort (part of the ongoing iGENE study).

OS08.4.A Retrospective analysis of in vivo 1H-magnetic resonance spectroscopy based on a machine learning approach enables reliable prediction of IDH mutation in patients with glioma

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii11-ii11
Author(s):  
E Bumes ◽  
C Fellner ◽  
S Lenz ◽  
R Linker ◽  
S Weis ◽  
...  
Keyword(s):  
Machine Learning ◽  
Validation Cohort ◽  
Resonance Spectroscopy ◽  
Learning Approach ◽  
Idh Mutation ◽  
1H Mrs ◽  
1H Magnetic Resonance Spectroscopy ◽  
Mutation Status ◽  
Machine Learning Approach

Abstract BACKGROUND Mutation of isocitrate dehydrogenase (IDH) is not only an important landmark in the development of low-grade gliomas, but also has prognostic significance and is a potential therapeutic target. There is a high need to determinate IDH mutation status at diagnosis and during the course of therapy in a non-invasive and reliable manner. We established a machine learning approach based on a support vector machine to detect IDH mutation status in in vivo standard 1H-magnetic resonance spectroscopy (1H-MRS) at 3T with an accuracy of 88.2%, a sensitivity of 95.5% (95% CI, 77.2–99.9%), and a specificity of 75% (95% CI, 42.85–94.5%) in a prospective monocentric clinical trial. Here, the same method is applied in a retrospective cohort at 1.5T and tested for transferability. MATERIAL AND METHODS Validation cohort. The validation cohort comprised 100 patients with glioma for which standard in vivo 1H-MRS spectra had been acquired between 2002 and 2007. Standard single voxel spectroscopy had been measured at 1.5T using a PRESS sequence with a TR of 1500ms and a TE of 30ms. One sample had to be excluded due to non-malignant histology and for 15 samples the IDH mutation status was not available. Therefore, the validation cohort comprised 84 samples, of which 35 were bearing an IDH mutation in immunohistochemistry (sequencing for confirmation is outstanding). Machine learning. To transfer our method to an independent validation cohort our previously established machine learning approach was first trained on all samples of the 3T group. The trained algorithm was then applied to the data of the validation cohort. Here, among other factors the different field strengths, with which the spectra were acquired (3T vs. 1.5T) had to be considered. RESULTS 27 samples of the validation cohort had to be excluded due to poor spectra quality. Our approach correctly detected IDH mutation status in 47 of 62 patients (75.8%), although the technical conditions were significantly different from our published prospective cohort. 17 of 30 patients bearing an IDH mutation were correctly identified, while 30 of 32 wild type patients were determined successfully. CONCLUSION Our approach to detect IDH mutation status has promising application in an unselected retrospective cohort, demonstrating transferability across different technical conditions. Further investigations to improve our technique and an advanced neuropathological processing of the samples are planned.

scholarly journals MEGF10, a Glioma Survival-Associated Molecular Signature, Predicts IDH Mutation Status

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Guanzhang Li ◽  
Zhiliang Wang ◽  
Chuanbao Zhang ◽  
Xing Liu ◽  
Fuqiang Yang ◽  
...  
Keyword(s):  
Promoter Region ◽  
Genetic Alterations ◽  
Primary Brain Tumor ◽  
The Cancer Genome Atlas ◽  
Molecular Signature ◽  
Common Mutation ◽  
Lower Grade ◽  
Idh Mutation ◽  
Mutation Status ◽  
Genome Atlas

Glioma is the most common primary brain tumor with various genetic alterations; among which, IDH mutation is the most common mutation and plays an important role in glioma early development, especially in lower grade glioma (LGG, WHO II-III). Previous studies have found that IDH mutation is tightly associated with extensive methylation across whole genome in glioma. To further investigate the role of IDH, we obtained methylation data of 777 samples from CGGA (Chinese Glioma Genome Atlas) and TCGA (The Cancer Genome Atlas) with IDH mutation status available. A package compiled under R language called Tspair was used as the main analytic tool to find potential probes that were significantly affected by IDH mutation. As a result, we found one pair of probes, cg06940792 and cg26025891, which was capable of predicting IDH mutation status precisely. The hypermethylated probe was cg06940792, designed in the promoter region of MEGF10, while the hypomethylated probe was cg26025891, designed in the promoter region of PSTPIP1. Survival analysis proved that hypermethylation or low expression of MEGF10 indicated a favorable prognosis in 983 glioma samples. Moreover, gene ontology analysis demonstrated that MEGF10 was associated with cell migration, cell proliferation, and regulation of apoptosis in glioma. All findings above can be validated in three other independent cohorts. In a word, our results suggested that methylation level and mRNA expression of MEGF10 in glioma were not only correlated with IDH mutation but also associated with clinical outcome of patients, providing potential guide for future dissection of IDH role in glioma.

scholarly journals Fully automated hybrid approach to predict the IDH mutation status of gliomas via deep learning and radiomics

2020 ◽  
Author(s):  
Yoon Seong Choi ◽  
Sohi Bae ◽  
Jong Hee Chang ◽  
Seok-Gu Kang ◽  
Se Hoon Kim ◽  
...  
Keyword(s):  
Hybrid Model ◽  
Hybrid Approach ◽  
University Hospital ◽  
Tumor Segmentation ◽  
Idh Mutation ◽  
Mr Images ◽  
Mutation Status ◽  
Severance Hospital ◽  
National University ◽  
Fluid Attenuated Inversion Recovery

Abstract Background Glioma prognosis depends on isocitrate dehydrogenase (IDH) mutation status. We aimed to predict the IDH status of gliomas from preoperative MR images using a fully automated hybrid approach with convolutional neural networks (CNNs) and radiomics. Methods We reviewed 1166 preoperative MR images of gliomas (grades II–IV) from Severance Hospital (n = 856), Seoul National University Hospital (SNUH; n = 107), and The Cancer Imaging Archive (TCIA; n = 203). The Severance set was subdivided into the development (n = 727) and internal test (n = 129) sets. Based on T1 postcontrast, T2, and fluid-attenuated inversion recovery images, a fully automated model was developed that comprised a CNN for tumor segmentation (Model 1) and CNN-based classifier for IDH status prediction (Model 2) that uses a hybrid approach based on 2D tumor images and radiomic features from 3D tumor shape and loci guided by Model 1. The trained model was tested on internal (a subset of the Severance set) and external (SNUH and TCIA) test sets. Results The CNN for tumor segmentation (Model 1) achieved a dice coefficient of 0.86–0.92 across datasets. Our hybrid model achieved accuracies of 93.8%, 87.9%, and 78.8%, with areas under the receiver operating characteristic curves of 0.96, 0.94, and 0.86 and areas under the precision-recall curves of 0.88, 0.82, and 0.81 in the internal test, SNUH, and TCIA sets, respectively. Conclusions Our fully automated hybrid model demonstrated the potential to be a highly reproducible and generalizable tool across different datasets for the noninvasive prediction of the IDH status of gliomas.

Intraoperative assessment of isocitrate dehydrogenase mutation status in human gliomas using desorption electrospray ionization–mass spectrometry

2020 ◽  
Vol 132 (1) ◽  
pp. 180-187 ◽  
Author(s):  
Clint M. Alfaro ◽  
Valentina Pirro ◽  
Michael F. Keating ◽  
Eyas M. Hattab ◽  
R. Graham Cooks ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Isocitrate Dehydrogenase ◽  
Tumor Resection ◽  
Desorption Electrospray Ionization ◽  
Extent Of Resection ◽  
Ionization Mass ◽  
Idh Mutation ◽  
Mutation Status ◽  
Desi Ms

OBJECTIVEThe authors describe a rapid intraoperative ambient ionization mass spectrometry (MS) method for determining isocitrate dehydrogenase (IDH) mutation status from glioma tissue biopsies. This method offers new glioma management options and may impact extent of resection goals. Assessment of the IDH mutation is key for accurate glioma diagnosis, particularly for differentiating diffuse glioma from other neoplastic and reactive inflammatory conditions, a challenge for the standard intraoperative diagnostic consultation that relies solely on morphology.METHODSBanked glioma specimens (n = 37) were analyzed by desorption electrospray ionization–MS (DESI-MS) to develop a diagnostic method to detect the known altered oncometabolite in IDH-mutant gliomas, 2-hydroxyglutarate (2HG). The method was used intraoperatively to analyze tissue smears obtained from glioma patients undergoing resection and to rapidly diagnose IDH mutation status (< 5 minutes). Fifty-one tumor core biopsies from 25 patients (14 wild type [WT] and 11 mutant) were examined and data were analyzed using analysis of variance and receiver operating characteristic curve analysis.RESULTSThe optimized DESI-MS method discriminated between IDH-WT and IDH-mutant gliomas, with an average sensitivity and specificity of 100%. The average normalized DESI-MS 2HG signal was an order of magnitude higher in IDH-mutant glioma than in IDH-WT glioma. The DESI 2HG signal intensities correlated with independently measured 2HG concentrations (R2 = 0.98). In 1 case, an IDH1 R132H–mutant glioma was misdiagnosed as a demyelinating condition by frozen section histology during the intraoperative consultation, and no resection was performed pending the final pathology report. A second craniotomy and tumor resection was performed after the final pathology provided a diagnosis most consistent with an IDH-mutant glioblastoma. During the second craniotomy, high levels of 2HG in the tumor core biopsies were detected.CONCLUSIONSThis study demonstrates the capability to differentiate rapidly between IDH-mutant gliomas and IDH-WT conditions by DESI-MS during tumor resection. DESI-MS analysis of tissue smears is simple and can be easily integrated into the standard intraoperative pathology consultation. This approach may aid in solving differential diagnosis problems associated with low-grade gliomas and could influence intraoperative decisions regarding extent of resection, ultimately improving patient outcome. Research is ongoing to expand the patient cohort, systematically validate the DESI-MS method, and investigate the relationships between 2HG and tumor heterogeneity.

scholarly journals Couples’ experiences with expanded carrier screening: evaluation of a university hospital screening offer

2021 ◽  
Author(s):  
Ivy van Dijke ◽  
Phillis Lakeman ◽  
Naoual Sabiri ◽  
Hanna Rusticus ◽  
Cecile P. E. Ottenheim ◽  
...  
Keyword(s):  
High Risk ◽  
Medical Center ◽  
Informed Choice ◽  
Carrier Screening ◽  
University Hospital ◽  
Structured Interviews ◽  
Expanded Carrier Screening ◽  
Post Test ◽  
Future Child ◽  
Clinically Significant

AbstractPreconception carrier screening offers couples the possibility to receive information about the risk of having a child with a recessive disorder. Since 2016, an expanded carrier screening (ECS) test for 50 severe autosomal recessive disorders has been available at Amsterdam Medical Center, a Dutch university hospital. This mixed-methods study evaluated the experiences of couples that participated in the carrier screening offer, including high-risk participants, as well as participants with a general population risk. All participants received genetic counselling, and pre- (n = 132) and post-test (n = 86) questionnaires and semi-structured interviews (n = 16) were administered. The most important reason to have ECS was to spare a future child a life with a severe disorder (47%). The majority of survey respondents made an informed decision (86%), as assessed by the Multidimensional Measure of Informed Choice. Among the 86 respondents, 27 individual carriers and no new carrier couples were identified. Turn-around time of the test results was considered too long and costs were perceived as too high. Overall, mean levels of anxiety were not clinically elevated. High-risk respondents (n = 89) and pregnant respondents (n = 13) experienced higher levels of anxiety before testing, which decreased after receiving the test result. Although not clinically significant, distress was on average higher for carriers compared to non-carriers (p < 0.0001). All respondents would opt for the test again, and 80.2% would recommend it to others. The results suggest that ECS should ideally be offered before pregnancy, to minimise anxiety. This study could inform current and future implementation initiatives of preconception ECS.

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