bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMG-05. THE T2-FLAIR MISMATCH SIGN IN IDH-MUTANT ASTROCYTOMAS - IS THERE AN ASSOCIATION WITH FET PET UPTAKE?
Authors: Galldiks Norbert , Werner Jan-Michael , Stoffels Gabriele , Kocher Martin , Tscherpel Caroline , Jain Rajan , Shah Nadim , Fink Gereon , Langen Karl-Josef , Lohmann Philipp 
Published: November 2019

Abstract

BACKGROUND
The purpose of this study was (i) to assess the reproducibility of the previously described T2-FLAIR mismatch sign as a highly specific MR imaging marker in non-enhancing IDH-mutant, 1p/19q non-codeleted lower-grade gliomas (LGG) of the WHO grades II or III, and (ii) its association with the uptake of the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) in PET to further metabolically characterize that sign, which is currently poorly understood.

METHODS
Consecutive MRI and dynamic FET PET scans (n=134) from newly diagnosed and neuropathologically confirmed IDH-mutant LGG (n=65) and IDH-wildtype gliomas as control group (n=69) were evaluated by two independent raters to assess presence/absence of the T2-FLAIR mismatch sign as well as FET uptake. Interrater agreement was assessed using Cohen’s kappa (κ), as well as diagnostic performance (i.e., positive/negative predictive value; PPV, NPV) of the T2-FLAIR mismatch sign to identify IDH-mutant astrocytomas.

RESULTS
In the LGG group, 13 patients (20%) had a T2-FLAIR mismatch sign, which could be identified with a substantial interrater agreement (κ=0.75). In contrast, that sign was absent in IDH-wildtype gliomas. All 13 cases that were positive for the T2/FLAIR mismatch sign were IDH-mutant, 1p/19q non-codeleted tumors (PPV=100%, NPV=57%). Interestingly, compared to IDH-mutant gliomas without the T2-FLAIR mismatch sign, the sign was significantly (P=0.027; 10 of 13 patients) associated with a negative FET PET scan (i.e., 5 tumors with indifferent FET uptake comparable to the background activity, or FET uptake below background activity (photopenic defect) in 5 tumors).

CONCLUSIONS
With a robust interrater agreement, our findings are in line with previously reported findings regarding the T2-FLAIR mismatch sign. Additionally, the T2-FLAIR mismatch sign seems to be significantly related with a lack of increased FET uptake in PET, which may help to further characterize patients with that sign. Notwithstanding, the clinical relevance of this imaging constellation warrants further investigation.
NIMG-30. REPRODUCIBLE RADIOMIC MAPPING OF TUMOR CELL DENSITY BY MACHINE LEARNING AND DOMAIN ADAPTATION
Authors: Wang Lujia , Yoon Hyunsoo , Hawkins-Daarud Andrea , Singleton Kyle , Clark-Swanson Kamala , Bendok Bernard , Mrugala Maciej , Eschbacher Jenny , Smith Kris , Nakaji Peter , Gonzalez Ashlyn , Nespodzany Ashley , Baxter Leslie , Wu Teresa , Swanson Kristin , Hu Leland , Li Jing 
Published: November 2019

Abstract

BACKGROUND
An important challenge in radiomics research is reproducibility. Images are collected on different image scanners and protocols, which introduces significant variability even for the same type of image across institutions. In the present proof-of-concept study, we address the reproducibility issue by using domain adaptation – an algorithm that transforms the radiomic features of each new patient to align with the distribution of features formed by the patient samples in a training set.

METHOD
Our dataset included 18 patients in training with a total of 82 biopsy sample. The pathological tumor cell density was available for each sample. Radiomic (statistical + texture) features were extracted from the region of six image contrasts locally matched with each biopsy sample. A Gaussian Process (GP) classifier was built to predict tumor cell density using radiomic features. Another 6 patients were used to test the training model. These patients had a total of 31 biopsy samples. The images of each test patient were purposely normalized using a different approach, i.e., using the CSF instead of the whole brain as the reference. This was to mimic the practical scenario of image source discrepancy between different patients. Domain adaptation was applied to each test patient.

RESULTS
Among the 18 training patients, the leave-one-patient-out cross validation accuracy is 0.81 AUC, 0.78 sensitivity, and 0.83 specificity. When the trained model was applied to the 6 test patients (purposely normalized using a different approach than that of the training data), the accuracy dramatically reduced to 0.39 AUC, 0.08 sensitivity, and 0.61 specificity. After using domain adaption, the accuracy improved to 0.68 AUC, 0.62 sensitivity, and 0.72 specificity.

CONCLUSION
We provide candidate enabling tools to address reproducibility in radiomics models by using domain adaption algorithms to account for discrepancy of the images between different patients.
NIMG-32. CHALLENGES OF IMAGING INTERPRETATION TO PREDICT OLIGODENDROGLIOMA GRADE
Authors: Aboud Orwa , Gilbert Mark , Armstrong Terri , Vera Elizabeth , Wu Jing , Wall Kathleen , Theeler Brett , Siegel Christine , Reyes Jennifer , Leggiero Nicole , Crandon Sonja , Cordova Christine , Boris Lisa , Bryla Christine , Burton Eric , Antony Ramya , Quezado Martha , Shah Ritu , Penas-Prado Marta 
Published: November 2019

Abstract

BACKGROUND
A recent report examining 75 Oligodendrogliomas indicated that specific imaging features may help predict grading and guide target selection for biopsy when resection is not possible. This report attempted to validate these findings in a separate sample and evaluate interrater reliability.

METHODS
Two Neuro-Oncologists, blinded to radiology report and grading reviewed diagnostic pre-radiation MRI. Imaging features and reviewer interpretations were evaluated included contrast enhancement, necrosis, calcification, and restricted diffusion; examiner concordance is reported.

RESULTS
Sixty-two patients with diagnosis of Oligodendroglioma (50 WHO grade II, 12 WHO grade III); 54 were molecularly confirmed as IDH-mutant/1p19q co-deleted based on the NOB Natural History Study. Four patients (grade III) were excluded due to lack of imaging studies. Among 58 evaluable patients, their location was frontal (n=32), temporal (n=14), parietal (n=4), occipital (n=1), and multi-lobe (n=11). Extent of resection: gross total 9, subtotal 36, biopsy 17. Partial to extensive contrast enhancement was present in 18/58 patients (6 grade II, 33%; 12 grade III, 67%); Kappa interrater agreement k= 0.37 on grade II and k=0.50 on grade III; extensive enhancement was present in 4/58 (all grade III), k= 0.70. Necrosis noted in 7/58 patients (all grade III), k=0.61. Calcification noted in 7/17 patients reviewed (all grade III), k=1.0; restriction noted in only 2/39 patients reviewed (all grade III), k=1.0.

CONCLUSIONS
THE presence of extensive enhancement, necrosis, calcification and restricted diffusion were only present in grade III with substantial agreement between readers, but there was lower agreement for partial enhancement. Image reviewers commented on the variability of enhancement intensity in normal structures between scans, likely contributing to this poor concordance. Tumor areas with extensive enhancement and/or necrosis are associated with higher grade and can guide biopsy if resection is not feasible. Discrepancies in imaging interpretation may be ameliorated by implementing a standardized imaging protocol.
NIMG-33. TUMOR GROWTH AND MRI TRAJECTORIES IN GRADE II AND III GLIOMA
Authors: Luks Tracy , Li Yan , Alcaide-Leon Paula , Lafontaine Marisa , Jakary Angela , Chang Susan , Villanueva-Meyer Javier 
Published: November 2019

Abstract

INTRODUCTION
The purpose of this work was to investigate the trajectory of tumor growth and multiparametric MRI characteristics in grade II and III gliomas leading up to the onset of new contrast enhancement or the expansion of FLAIR signal abnormality.

METHODS
Fifty-one grade II and III glioma patients (39 grade II, 12 grade III) underwent serial MR imaging at standard of care timepoints. Multiparametric MR imaging was performed and maps of the apparent diffusion coefficient (ADC) and percentiles (10th, 50th, 90th) from histograms of normalized signal intensities were calculated. Regions of Interest (ROIs) were defined for the entire T2/FLAIR lesion, and when present, the contrast-enhancing (CE) lesion. Serial imaging parameters were acquired for each of these ROIs. Linear rates of change were calculated for CE volume, T2/FLAIR volume, normalized T2 FSE intensity within the FLAIR volume, normalized T2/FLAIR intensity within the FLAIR volume, and normalized median, 10th percentile and 90th% ADC values within the FLAIR volume.

RESULTS
Thirty-nine patients progressed while on study (7 by CE growth, 32 by T2/FLAIR growth), and 12 patients remained stable, according to RANO criteria. In progressed patients, T2/FLAIR volume and T2 FSE intensity increased over time to progression. The rate of T2/FLAIR volume growth was significantly greater in progressed than stable patients (mean = .42, -.07 mL/week, respectively). The rate of normalized T2/FLAIR signal intensity change was also significantly different in progressed than stable patients (mean = -.002, .0035 mL/week). There were no significant interactions with grade or molecular subgroup by WHO criteria. Additionally, 44% (17/39) of progressed patients by RANO criteria were characterized as having stable disease by radiologic assessment.

CONCLUSION
Tumor volumes remain the gold standard for response assessment in lower grade gliomas and there exists a need for standardized measurement as visual assessment for determination of tumor status is inconsistent.
NIMG-43. LONGITUDINAL TRACKING AND GROWTH RATE CHARACTERIZATION OF BRAIN METASTASES ON MAGNETIC RESONANCE IMAGING
Authors: Patel Jay , Beers Andrew , Chang Ken , Brown James , Hoebel Katharina , Rosen Bruce , Huang Raymond , Brastianos Priscilla , Gerstner Elizabeth , Kalpathy-Cramer Jayashree 
Published: November 2019

Abstract

PURPOSE
Measuring treatment response is vital for assessing efficacy of treatment regimen for patients with brain metastases (BM). Unfortunately, manual delineation of all lesions on MRI across time-points is prohibitively time-consuming, making it infeasible to track individual lesion growth/shrinkage rates as part of the clinical workflow. To overcome this challenge, we propose a deep learning approach to segment all BM, and furthermore, show that certain brain regions are more prone to high-growth rate lesions.

METHODS
163 longitudinal MRIs from 77 patients with MPRAGE-post contrast imaging protocol were prospectively obtained from Massachusetts General Hospital (MGH). An expert neuro-oncologist provided ground truth segmentations for all patients. A 3D U-Net architecture was trained to automatically segment BM; training was stopped when validation set Dice score plateaued to prevent overfitting. To enable lesion tracking, all time-points per patient were affinely registered to each other. Every lesion was subsequently classified based on its growth rate (responder: overall lesion shrinkage; inconclusive: 0% to 40% lesion growth; non-responder: more than 40% lesion growth). Characterization of global lesion growth rate patterns was accomplished by affinely registering all time-points to the MNI brain atlas. Segmented lesions were projected onto the atlas, which was qualitatively analyzed to identify spatial regions composed primarily of one class of lesion.

RESULTS
For automatic segmentation, we report a mean dice score of 0.778, 0.737, and 0.704 on training, validation, and testing sets respectively. Furthermore, we find that the largest BM with the highest average growth rate (non-responders) tend to be located in the posterior frontal/parietal lobes, while smaller, lower growth rate lesions (responders) tend to be localized in the frontal lobes. The posterior fossa was found to be heterogeneous in lesion size and growth rate.

CONCLUSION
We developed automatic metastatic lesion tracking over time-points and identified brain regions associated with differing growth rate lesions.
NIMG-66. LONG-TERM FOLLOW-UP OF NEUROFIBROMATOSIS TYPE 1 PATIENTS USING WHOLE-BODY MRI DEMONSTRATES DYNAMIC CHANGES IN INTERNAL NEUROFIBROMA SIZE
Authors: Ly Ina , Thalheimer Raquel , Cai Wenli , Bredella Miriam , Merker Vanessa , Plotkin Scott , Jordan Justin 
Published: November 2019

Abstract

BACKGROUND
Neurofibromas affect 40–50% of neurofibromatosis type 1 (NF1) patients and can cause significant morbidity and mortality. They grow more rapidly during childhood and adolescence but studies in adults are limited by their retrospective nature and follow-up time < 3 years. The long-term natural history of neurofibromas remains unknown. No guidelines exist on the need and frequency of surveillance imaging for patients. Whole-body MRI (WBMRI) can detect whole-body tumor burden, including internal neurofibromas.

METHODS
17 adult NF1 patients who underwent WBMRI between 2007–2010 (Scan 1) underwent repeat WBMRI between 2018–2019 (Scan 2). Internal neurofibromas were segmented on short tau inversion recovery (STIR) sequences and tumor volume was calculated using a computerized volumetry and three-dimensional segmentation software. Circumscribed tumors were defined as discrete; invasive tumors or those involving multiple nerves were defined as plexiform. Tumor growth and shrinkage were defined as volume change ≥ 20% over the entire study period.

RESULTS
Median patient age was 43 years during Scan 1 and 53 years during Scan 2. Median time between Scan 1 and 2 was 9 years. A total of 140 neurofibromas were assessed. 24% of tumors grew by a median 63% (6.8% per year). 54% of tumors spontaneously decreased in volume by a median 60% (7% per year) without treatment. On a per-patient basis, 18% of patients had overall tumor growth and 41% overall tumor shrinkage. 8 new tumors developed in 7 patients. 16 tumors resolved entirely without medical or surgical intervention. Growth behavior did not correlate with discrete or plexiform morphology.

CONCLUSION
A subset of internal neurofibromas in adult NF1 patients grow significantly over a long-term period, suggesting that continued monitoring of these patients may be warranted. Surprisingly, more than half of neurofibromas shrink spontaneously without intervention. Continued patient enrollment and correlation of imaging findings with functional outcomes are underway.
NCMP-06. THE INCIDENCE OF POST-IRRADIATION CAVERNOUS ANGIOMA AND CYSTIC MALACIA AFTER HIGH DOSE CRANIAL IRRADIATION IN PEDIATRIC AND ADULT MALIGNANT BRAIN TUMORS
Authors: Taniguchi Hiroki , Yamasaki Fumiyuki , Takano Motoki , Yonezawa Ushio , Sugiyama Kazuhiko , Kurisu Kaoru 
Published: November 2019

Abstract

PURPOSE
The purpose of this study is to investigate the incidence of cavernous angioma (CVA) and cystic malacia in long-term survivors of pediatric and adult malignant brain tumors treated by cranial irradiation.

MATERIALS AND METHODS
36 pediatric (age < 18, M:F=24:12, mainly consisted of embryonal tumors) and 43 adults (age ≥18,M:F=27:16, mainly consisted of gliomas) patients with malignant tumors receiving high dose cranial irradiation and at least three years disease free period were included in this study. Follow-up of adult patients ranged from 3.2–19.4 years (median 7.6 years), the local irradiation dose from 50 to 60Gy. Follow-up of pediatric patients ranged from 3.8–18.4 years (median 9.0 years), the local irradiation dose from 49.6 to 60.4Gy. All patients underwent follow-up magnetic resonance imaging studies at least once a year, and the diagnosis of post-treatment CVA and cystic malacia was based solely on MRI findings.

RESULTS
At the timing of preparing this abstract, 16 adult patients developed CVAs during the median course of 13 years, while 24 pediatric patients developed CVAs during the median course of 5.8 years, and the difference was significant (P=0.0298, log-rank test). While, there was no statistical difference between adult and pediatric patients for the development of Zabramski type 1 & 2 CVAs, or of cystic malacia (P=0.6254 and P=0.4652, respectively).

CONCLUSION
We attribute the high rate of post-RT CVAs in our long-term follow-up study of adult patients to the delivery of cranial irradiation for glioma patients. Our data imply the importance of long term follow-up not only for pediatric patients but also for adult patients after high dose cranial irradiation.
NCMP-10. OUTCOMES WITH ACYCLOVIR TREATMENT IN HERPES SIMPLEX ENCEPHALITIS AFTER SURGERY FOR SOLID CNS TUMORS: A CASE REPORT AND SYSTEMATIC REVIEW OF THE LITERATURE
Authors: Ambe Solomon , Yari Niloofar , Fonkem Ekokobe , Benardete Ethan , Chen Wencong 
Published: November 2019

Abstract

OBJECTIVE
To characterize the incidence, diagnostic and therapeutic trends and raise awareness of cases of Herpes Simplex Encephalitis occurring within 30 days after neurosurgery for CNS tumors.

METHOD
Literature search for cases meeting above criteria and meta-analysis of data.

RESULTS
18 cases were studied. The most common tumor was meningitis. Encephalopathy, fever and seizure were the most common presenting symptoms (94%, 83% and 50 % respectively). 50% of cases had HSV-1, 22% had HSV-2, while 28% were unspecified. A majority of the patients (78%) received in acyclovir, with a 79% survival rate with treatment. Mortality rate was 100% without acyclovir treatment. Median time of starting acyclovir was 17 days. Most patients received steroids (78%) but steroids was not associated with a specific outcome.

CONCLUSION
Herpes simplex Encephalitis should be suspected after neurosurgery for tumors in patients with fever, encephalopathy or seizures and should be promptly treated with iv acyclovir. A delay in recognition and failure to treat could result in severe morbidity and mortality. In our study steroid use was not associated with improved outcome but larger studies are needed.
PDTC-17. A RETROSPECTIVE STUDY OF RECOMBINANT HUMAN ENDOSTATIN COMBINED WITH CARBOPLATIN AND VINCRISTINE FOR PEDIATRIC LOW-GRADE GLIOMAS
Authors: Zhang Jun-Ping 
Published: November 2019

Abstract

OBJECTIVE
To analyze the response and toxicity of recombinant human endostatin (rh-ES) combined with carboplatin and vincristine (CV) chemotherapy regimen for pediatric low-grade gliomas (LGGs).

METHODS
Retrospectively reviewed the clinical data of the patients who were received rh-ES with CV chemotherapy regimen at Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University from October 2014 to October 2018. Carboplatin was administrated at a dose of 200~300 mg/m2 and the vincristine dose was 1.5 mg/m2 (maximum dose: 2 mg). Rh-ES was administrated 15 mg/d, daily for 14 days of each 28-day treatment cycle.

RESULTS
26 patients were enrolled. By the time of the last follow-up, 14 patients had completed the treatment and 6 were still in treatment. Of the 26 patients, 14 had partial response (PR), 12 had stable disease (SD), and the objective response rate (ORR) was 53.8%. Of the 14 patients who completed all the treatment, 10 achieved PR, 4 got SD, and the ORR was 71.4%. The median time interval to response was 3.3 months (range 2–12.6 months). The main adverse reactions were myelosuppression and allergy to carboplatin. Three patients were terminated in the consolidation phase due to adverse reactions.

CONCLUSIONS
The rh-ES combined with CV regimen is effective in the treatment of pediatric LGGs and had a rapid time interval to response, which is conducive to the rapid relief of brain stem or visual function damage.
PDTM-05. SONIC HEDGEHOG SIGNALING PRIMES CEREBELLAR GRANULE NEURON PROGENITORS AND MEDULLOBLASTOMA CELLS FOR APOPTOSIS BY INDUCING PRO-APOPTOTIC BIM
Authors: Cleveland Abigail , Veleta Katherine , Gershon Timothy 
Published: November 2019

Abstract
Medulloblastomas, unlike other malignant brain tumors, are typically sensitive to radiation therapy (xRT). However, although xRT allows medulloblastoma patients to survive, it can also confer significant long term cognitive sequelae. Understanding the mechanisms of radiation sensitivity in medulloblastoma may identify ways to increase this sensitivity through targeted therapy. Cerebellar granule neuron progenitors (CGNPs), the cells of origin for SHH-subgroup medulloblastoma, are also sensitive to xRT. We have shown that SHH signaling, which induces CGN proliferation and in excess can cause medulloblastoma, induces the pro-apoptotic protein BIM, resulting in increased radiation sensitivity. SHH-stimulated CGNPs show robust BIM expression, which is blocked by the SMO inhibitor vismodegib. CGNPs in BIM null mice show normal SHH-driven proliferation, but are markedly less sensitive to radiation. Protein studies show that BIM binds to the anti-apoptotic proteins BCL-xL and MCL-1, suggesting a mechanism for increasing the sensitivity to radiation by lowering the apoptotic threshold. On-going studies will determine whether BIM is required for radiation sensitivity in SHH-driven medulloblastoma. If validated, the BIM interactions with BCL-xL and MCL-1 may be novel mechanisms to be targeted to improve medulloblastoma therapy.
PDTM-13. A NOVEL DIFFUSE MIDLINE GLIOMA MODEL INITIATED IN OLIG2-EXPRESSING PROGENITORS OF THE NEONATAL BRAIN
Authors: Shimazu Yosuke , Somasundaram Agila , Brat Daniel , Becher Oren 
Published: November 2019

Abstract
Diffuse intrinsic pontine glioma (DIPG) is an incurable brain tumor that arises in the pons of children. Recent studies using single cell RNA-seq and enhancer analysis of DIPG tumor cells, together with analysis of the developing human pons, strongly suggest that an oligodendrocyte progenitor cell is the most likely cell-of-origin for DIPG. Here we describe a novel mouse model by expressing PDGF-B, with H3.3K27M or H3.3 wild-type in Olig2-expressing progenitors via injection into the 4th ventricle using Olig2-tva-cre;p53fl/fl mice. H3.3K27M tumors have high rate of Ki-67, Sox2, and Olig2 positivity and show a higher rate of leptomeningeal dissemination than H3.3 wild-type tumors (95.2％ vs 68.8%, p=0.0303) and mice harboring H3.3K27M tumors demonstrate a significantly shorter survival period than those harboring H3.3 wild-type tumors (31 days vs. 37 days, p=0.0473). While there is not any difference in survival between mice harboring PDGF-B; p53 wild-type; H3.3K27M tumors and those harboring PDGF-B; p53 wild-type; H3.3 wild-type tumors at the 6-month endpoint, we found that H3.3K27M tumors show a higher rate of high-grade glioma than H3.3 wild-type tumors (100% vs. 41.7%, p=0.0017). RNA-seq analysis identified 25 significantly differentially expressed genes with 23 upregulated and 2 downregulated genes in the PDGF-B; p53 null; H3.3K27M tumors compared with the H3.3 wild-type tumors. Phox2b, which is the most upregulated gene in the PDGF-B; p53 null; H3.3K27M tumors, was validated by qRT-PCR and expressed only in brainstem tumors and not expressed in tumors located in any other areas. IHC with Phox2b also revealed positivity in PDGF-B; p53 null; H3.3K27M tumors located only in the brainstem. Ongoing work includes validation of other significant differentially expressed genes as well as elucidation of their role in K27M-mediated gliomagenesis.