bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMG-02. 18F-FLUCICLOVINE PET/CT TO DISTINGUISH RADIATION NECROSIS FROM TUMOR PROGRESSION IN BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY
Authors: Tom Martin , DiFilippo Frank , Jones Stephen , Suh John , Murphy Erin , Yu Jennifer , Mohammadi Alireza , Barnett Gene , Huang Steve , Wu Guiyun , Obuchowski Nancy , Ahluwalia Manmeet , Peereboom David , Stevens Glen , Chao Samuel 
Published: December 2020

Abstract

PURPOSE/OBJECTIVE(S)
To report descriptive updates of an ongoing pilot trial assessing whether 18F-Fluciclovine PET/CT, a widely available amino-acid radiotracer, is useful to distinguish radiation necrosis (RN) from tumor progression (TP) among patients with brain metastases.

MATERIALS/METHODS
The primary objective is to estimate the accuracy of 18F-Fluciclovine PET/CT in distinguishing RN from TP. We included adults with brain metastases who underwent prior stereotactic radiosurgery and presented with a follow-up MRI brain (with DSC-MR perfusion) which was equivocal for RN versus TP. Within 30 days of equivocal MRI, patients underwent 18F-Fluciclovine PET/CT on a Siemens Biograph mCT scanner with a 10 mCi bolus dose immediately prior to PET. PET data were collected in list-mode for 25 mins post-injection and were reconstructed as a static image of data 10-25 mins post-injection, and as a dynamic series of four 5-min frames between 5-25 mins post-injection. Quantitative metrics for each lesion were documented. Lesion to normal brain ratios were calculated. The reference standard was clinical follow-up with MRI brain (with DSC-MR perfusion) every 2-4 months until multidisciplinary consensus (or tissue confirmation) for diagnosis of RN versus TP.

RESULTS
From 7/2019-6/2020, 12 of 16 planned subjects with 17 lesions underwent 18F-Fluciclovine PET/CT. Primary histology was non-small cell lung cancer in 5 patients, breast in 4, melanoma in 2, and endometrial in 1. Among all 17 lesions, ranges of quantitative metrics were: SUVmax, 2.18-12.10; SUVmean, 1.16-7.37; SUVpeak, 1.06-4.45; normal brain SUVmean, 0.19-0.44; SUVmax/normal ratio, 7.50-45.40; SUVmean/normal ratio, 4.20-26.30; and SUVpeak/normal ratio, 3.90-26.40. Follow-up was completed for 5 patients (6 lesions). No adverse events have occurred.

CONCLUSION
In this population, 18F-Fluciclovine produces a wide range of lesion quantitative metric values and uniformly low uptake in normal brain, which may allow accurate discrimination. Ongoing additional accrual and follow up is required.
NIMG-05. ADVANCED IMAGING TO ASSESS LONGITUDINAL VASCULAR CHANGES IN BRAIN METASTASES TREATED WITH CHECKPOINT INHIBITION
Authors: Kim Albert , Cardona Jonathan , Chang Ken , Beers Andrew , Brown James , Emblem Kyrre , Kalpathy-Cramer Jayashree , Lee Eudocia , Lin Nancy , Tolaney Sara , Nayak Lakshmi , Chukwueke Ugonma , Oh Kevin , Shih Helen , White Michael , Lawrence Donald , Moy Beverly , Cohen Justine , Giobbie-Hurder Anita , Cahill Daniel , Sullivan Ryan , Brastianos Priscilla , Gerstner Elizabeth 
Published: December 2020

Abstract
Immune checkpoint inhibitors (ICI) have recently been shown to be effective for brain metastases (BM) in melanoma and lung cancer. However, accurately assessing intracranial response in patients undergoing ICI is a challenge, as current measures cannot reliably distinguish pseudoprogression from true tumor progression. To identify potential biomarkers of response, we analyzed standard post-contrast and dynamic susceptibility contrast MRI to identify characteristic vascular signatures as part of an ongoing Phase 2 study of pembrolizumab for patients with untreated or progressive, previously treated BM from any histology. Tumor volume measurements were calculated by summating all enhancing voxels. A volumetric increase of &gt;40% was categorized as progressive disease (PD), a decrease of &gt;60% as partial response (PR), and stable disease (SD) as between -60% and +40%. 78 patients have been enrolled, of whom 44 have received at least baseline advanced MR imaging. Histologies include 21 with breast cancer, 5 with non-small cell lung cancer, 4 with melanoma, and 13 with other cancers. At baseline, the total number of BM was 1-50+ per patient. Based on summing the entire enhancing intracranial disease burden, best volumetric responses for the 33 evaluable patients include 4 PR, 10 SD, and 19 PD. On preliminary analysis, there was a correlation between increased tumor cerebral blood volume/flow with tumor progression. Correlation of additional vascular physiologic parameters (e.g. vessel caliber, tissue oxygenation) to volumetric response, patient outcome, and standardized response criteria (iRANO) are ongoing. Our data provides potential evidence that effective ICI is associated with a decrease in perfusion. Ongoing analyses to uncover additional vascular changes – specifically longitudinal metrics reflecting vascular structure and function - within BM to ICI are pending. These findings have potential to explore mechanisms of ICI response and resistance, as well as biomarkers of response.
NIMG-07. LONG-TERM FOLLOW-UP OF SCHWANNOMA GROWTH BEHAVIOR IN ADULT NEUROFIBROMATOSIS TYPE 2 AND SCHWANNOMATOSIS PATIENTS USING WHOLE-BODY MRI
Authors: Ly Ina , Thalheimer Raquel , Cai Wenli , Bredella Miriam , Muzikansky Alona , Merker Vanessa , Herr Hamilton , Da Jennifer , Harris Gordon , Plotkin Scott , Jordan Justin 
Published: December 2020

Abstract

BACKGROUND
Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are related genetic tumor predisposition syndromes caused by distinct germline pathogenic variants on chromosome 22. Both conditions are characterized by the presence of cranial, peripheral, and/or spinal nerve schwannomas. The long-term growth behavior of schwannomas is unknown but knowledge thereof would help guide patient surveillance and selection for treatment and improvement of clinical trial design. Whole-body MRI (WBMRI) can detect whole-body schwannoma burden in a single image acquisition session.

METHODS
12 NF2 and 10 SWN patients who underwent a WBMRI between 2007-2010 underwent a repeat WBMRI between 2018-2019. Schwannomas were segmented on short tau inversion recovery (STIR) sequences. Tumor volume was calculated using a three-dimensional tumor quantification software (3DQI). Tumor growth and shrinkage were defined as a volume change ≥ 20% over the entire study period.

RESULTS
Median time between scans was 10 years. A total of 103 schwannomas (46 NF2-associated, 57 SWN-associated) were analyzed. In both NF2 and SWN, 50% of tumors grew. Median growth was 88.3% in NF2 and 100.4% in SWN. All growing NF2-associated schwannomas grew in the setting of exposure to systemic therapy whereas only one growing SWN-associated tumor had been treated systemically. Excluding resected tumors, 19.4% of schwannomas shrank. Median shrinkage was 48.5% in NF2 and 37.4% in SWN. All shrinking NF2-associated tumors had been treated with systemic therapy whereas none of the shrinking SWN-associated tumors had been. 19 new tumors (7 NF2-associated, 12 SWN-associated) developed in 8 patients.

CONCLUSIONS
Half of NF2- and SWN-associated schwannomas grow significantly over a decade. In NF2 patients, growth occurs despite systemic treatment whereas, in SWN patients, schwannomas may shrink spontaneously without treatment. These findings may suggest a more aggressive tumor phenotype in NF2. Continued patient enrollment and correlation of MRI findings with functional outcomes and hormone exposure history are ongoing.
NIMG-16. EXPLORATORY EVALUATION OF Q-SPACE TRAJECTORY IMAGING PARAMETERS AS NOVEL IMAGING BIOMARKERS FOR GLIOMAS
Authors: Juvekar Parikshit , Szczepankiewicz Filip , Noh Thomas , Westin Carl-Fredrik , Golby Alexandra 
Published: December 2020

Abstract
Neuroimaging offers a non-invasive means to probe tumor tissue in order to inform decision making at all phases of brain tumor treatment. Diffusion MRI is particularly sensitive to tumor tissue microstructure, with greater heterogeneity being reflected as a larger diffusional kurtosis. Q-Space Trajectory Imaging (QTI) uses tensor-valued diffusion encoding (encoding along multiple directions per shot) to disentangle Isotropic Mean Kurtosis (MKi) from Anisotropic Mean Kurtosis (MKa), which are otherwise conflated in the Total Mean Kurtosis (MKt). To test whether disentangling MKi and MKa facilitates a more specific probe of tumor tissue heterogeneity and malignancy, we investigated if QTI parameters could distinguish low- from high-grade gliomas and enhancing from non-enhancing regions using pre-operative QTI imaging of 13 W.H.O. grade I-II and 18 grade III-IV glioma patients. We also analyzed these features separately for de novo and recurrent tumors. Regions of Interest (ROIs) were drawn on QTI maps, with support from T1 and T2-weighted images, for enhancing region, non-enhancing region, necrotic cavity, cyst, edema and resection cavity. ROC was used to gauge QTI parameter performance in classifying tumor characteristics. MKi was found to be the strongest predictor of tumor grade (AUC = 0.74, p = 0.019). MKi and MKt separated de novo from recurrent tumors (AUC = 0.80 and 0.76, p &lt; 0.05). MKt separated enhancing regions from non-enhancing regions with an AUC of 0.88 in all tumors and 0.97 in de novo tumors. Our preliminary results highlight that tensor-valued diffusion MRI and QTI analysis have the potential to non-invasively characterize tumor grade. Further, MKt accurately differentiated enhancing from non-enhancing tumors and could potentially substitute for gadolinium injection in some situations thereby decreasing risk, time, and cost. Our ongoing studies in larger groups aim to further correlate molecular tumor markers (eg. IDH1 status) with these diffusion parameters.
NIMG-20. MULTI-HABITAT RADIOMICS UNRAVELS DISTINCT PHENOTYPIC SUBTYPES OF GLIOBLASTOMA WITH CLINICAL AND GENOMIC SIGNIFICANCE
Authors: Won Choi Seung , Cho Hwan-ho , Koo Harim , Cho Kyung rae , Nenning Karl-Heinz , Langs Georg , Furtner Julia , Baumann Bernhard , Woehrer Adelheid , Cho Hee Jin , Kong Doo-Sik , Seol Ho Jun , Lee Jung-il , Nam Do-Hyun , Park Hyunjin 
Published: December 2020

Abstract

BACKGROUNDS
We aimed to evaluate the potential of radiomics as an imaging biomarker for GBM patients and explore the molecular rationale behind radiomics by radio-genomics approach.

METHODS
A total of 144 primary GBM patients were included in this study as a training cohort. Using multi-parametric MR images, radiomics features were extracted from multi-habitats of the tumor. We applied Cox-LASSO algorithm to build a survival prediction model and validated this model using an independent validation cohort (56 patients from Vienna). With the selected radiomics features, GBM patients were consensus clustered to reveal inherent phenotypic subtypes. The subtypes were further explored in terms of genomic signatures.

RESULTS
GBM patients were successfully stratified by the radiomics risk score, a weighted sum of radiomics features, corroborating the potential of radiomics as a prognostic biomarker. Using consensus clustering, we identified three distinct subtypes which significantly differed in the prognosis (‘heterogenous enhancing’, ‘rim-enhancing necrotic’, and ‘cystic’ subtype). Multi-variate cox regression analysis confirmed that radiomics subtype as an independent prognostic factor. Transcriptomic traits enriched in individual subtypes were in accordance with imaging phenotypes summarized by radiomics. For example, rim-enhancing necrotic subtype was well described by radiomics profiling (T2 autocorrelation & flat shape) and highlighted by the inflammatory genomic signatures, which well correlated to its phenotypic peculiarity (necrosis).

CONCLUSIONS
The present study confirmed the feasibility of radiomics as an imaging biomarker for GBM patients with comprehensible biologic annotation. Imaging subtypes derived from radiomics successfully recapitulate the genomic underpinnings of GBM tumors and in turn reinforce their potential as a prognostic biomarker.
NIMG-34. QUANTITATIVE MR PARAMETERS FOR THE PREDICTION OF EGFR AMPLIFICATION AND THE TERT PROMOTER MUTATION STATUS OF IDH-WILDTYPE LOWER-GRADE GLIOMAS
Authors: Won Park Yae , Ahn Sung Soo , Kim Eui Hyun , Kang Seok-Gu , Chang Jong Hee , Kim Se Hoon , Lee Seung-Koo 
Published: December 2020

Abstract

OBJECTIVES
To assess the predictive role of quantitative MRI parameters from DTI, dynamic susceptibility contrast (DSC), and dynamic contrast-enhanced (DCE) imaging in determining the epidermal growth factor receptor (EGFR) amplification and telomerase reverse transcriptase promoter (TERTp) mutation status of isocitrate dehydrogenase-wildtype (IDHwt) lower-grade gliomas (LGGs).

METHODS
A total of 49 patients with IDHwt LGGs with either known EGFR amplification (39 EGFR non-amplified, 10 EGFR-amplified) or TERTp mutation (19 TERTp wildtype, 21 TERTp mutant) statuses underwent preoperative MRI. The mean apparent diffusion coefficient (ADC), fractional anisotropy (FA), normalized cerebral blood volume (nCBV), normalized cerebral blood flow (nCBF), volume transfer constant (Ktrans), rate transfer coefficient (Kep), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp) values were assessed. Univariate and multivariate logistic regression models were constructed to predict EGFR amplification and TERTp status.

RESULTS
EGFR-amplified tumors showed lower mean ADC values than EGFR non-amplified tumors (p = 0.019). Mean ADC was an independent predictor of EGFR amplification, with an AUC of 0.75. TERTp mutant tumors showed higher mean nCBV (p = 0.020), higher mean nCBF (p = 0.017), and higher mean Vp (p = 0.002) than TERTp wildtype tumors. With multivariate logistic regression, mean Vp was the only independent predictor of TERTp mutation status, with an AUC of 0.85.

CONCLUSION
Lower ADC values may be a useful marker for the prediction of EGFR amplification, whereas higher Vp values may be a useful marker for the prediction of the TERTp mutation status of IDHwt LGGs.
NIMG-49. VALIDATION OF SIMULTANEOUS PH- AND O2-WEIGHTED MOLECULAR MRI USING 18F-FDG PET, IMMUNOHISTOCHEMISTRY, AND BIOENERGETICS
Authors: Hagiwara Akifumi , Yao Jingwen , Raymond Catalina , Morrow Danielle , Mareninov Sergey , Chun Saewon , Nathanson David , Yong William , Czernin Johannes , Divakaruni Ajit , Everson Richard , Patel Kunal , Salamon Noriko , Pope Whitney , Nghiemphu Phioanh , Liau Linda , Cloughesy Timothy , Ellingson Benjamin 
Published: December 2020

Abstract
This study aimed to investigate the potential of a novel MRI metric related to aerobic glycolysis in patients with diffuse gliomas. All subjects (Study I–III; 7, 26, and 11 subjects, respectively) were scanned on 3-T systems and underwent pH-weighted amine chemical exchange saturation transfer spin-and-gradient-echo echoplanar imaging (CEST-SAGE-EPI) or CEST-EPI, and perfusion imaging. Relative oxygen extraction fraction (rOEF) was calculated by dividing hypoxia-sensitive R2’ by normalized relative cerebral blood volume (nrCBV); a novel metric that characterizes glycolytic status (aerobic glycolytic index, AGI) was calculated by dividing amine CEST contrast by rOEF. Patients in Study I were additionally scanned by 18F-fluorodeoxyglucose (FDG)-PET. Stereotactic image-guided biopsies were performed on patients in Study II and III, and samples were analyzed by immunohistochemistry (IHC) and extracellular flux bioenergetic analysis, respectively. Pairwise correlation between MR metrics and standardized uptake value of 18F-FDG, IHC metrics, or indices of cellular metabolism was calculated using Spearman’s correlation analysis. In Study I, AGI showed very strong significant correlation with 18F-FDG uptake in glioma (correlation coefficient ρ = 0.86, P =0.014). In Study II, AGI was significantly correlated with glucose transporter 3 (ρ = 0.71; P = 0.0041) and hexokinase 2 (ρ = 0.73; P = 0.0029) in IDH wild-type glioma, while it was significantly correlated with monocarboxylate transporter 1 (ρ = 0.59; P = 0.0094) in IDH mutant glioma. This result may reflect the different glycolytic statuses of these gliomas; specifically, the rate-limiting steps in glycolysis. In Study III, a strong significant correlation with cellular AGI derived from the bioenergetic analysis was found for AGI derived from MRI (ρ = 0.79, P = .036). In conclusion, AGI derived from MRI was correlated with FDG, IHC measurements, and cellular AGI. Future studies investigating the clinical utility of AGI in prediction and evaluation of treatment effects are warranted.
NIMG-55. A QUANTITATIVE ANALYSIS OF BRAIN VOLUME DYNAMICS IN PCNSL PATIENTS TREATED WITH HIGH-DOSE METHOTREXATE-BASED THERAPY
Authors: Sivakumar Ananyaa , Kamson David , Estephan Fayez , Lambrecht Sebastian , Dzaye Omar , Wagner-Johnston Nina , Swinnen Lode , Gladstone Douglas , Lin Doris , Grossman Stuart , Holdhoff Matthias 
Published: December 2020

Abstract

BACKGROUND
Primary CNS lymphoma (PCNSL) is a rare, infiltrative disease. High-dose methotrexate (HD-MTX) is the backbone of induction regimens for PCNSL. While MTX-associated white matter changes are well-described, treatment-related brain volume loss is much less understood, especially in radiotherapy-naïve cohorts. Here, we aimed to longitudinally quantify the rates of brain volume loss in PCNSL patients treated with HD-MTX.

SUBJECTS/METHODS
We included 12 radiotherapy-naïve patients (age mean±SD 61±15y, range 37-84y, 9F) with histopathologically confirmed PCNSL who received HD-MTX induction (mean±SD 12±4 cycles, range 8-18) +/-rituximab. MRIs were collected from within 1 month of HD-MTX initiation until the end of follow-up (mean±SD: 3.7±2.9y). Longitudinal whole-brain segmentation was performed on FLAIR images using the Sequence Adaptive Multimodal Segmentation tool of FreeSurfer. Brain volumes were normalized to the initial scan, white matter lesion volumes were normalized to cerebral volume (nWML).

RESULTS
The average rate of cerebral volume change was -2.1±1.9%/year. Half of patients showed marked cerebral volume loss in the first year (-5.6±1.4% vs. -2.0±1.4%; n=10; p=0.003) with the most prominent change occurring within 6-months of treatment initiation (-4.2±1.7% vs. -0.5±1.6; n=12; p=0.004). Cerebral volume loss reached a plateau after the 1-year mark in both groups (0.3±0.8%/year vs. 1.4±3.3%/year; n=8; p=0.4). Patients younger than 61 years exhibited markedly higher rates of cerebral volume loss (-6.2±1.1%/year vs. 2.4±1.5%/year p=0.003), which was corroborated by strong inverse correlation between age and cerebral volume loss (Pearson’s r=-0.82, p=0.004). Neither the cerebellar volume, nor the nWML load correlated with age.

CONCLUSION
In the present cohort, brain volume loss was approximately four-fold higher than what is described in the healthy aging. Younger patients treated with HD-MTX exhibited more severe cerebral volume loss, which may be due to higher initial brain volume reserve. Detailed analyses of a larger sample are underway.
NIMG-60. ATYPICAL POSTERIOR REVERSIBLE LEUKOENCEPHALOPATHY SYNDROME MIMICKING TUMOR IN 1ST TRIMESTER PREGNANCY-’DON’T BELIEVE EVERYTHING YOU SEE’
Authors: Vishwanath Humsini , Shivaprasad Akhil , Tremont-Lukats Ivo , Powell Suzanne 
Published: December 2020

Abstract
Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiographic diagnosis characterized by headache, confusion, visual disturbances, seizures and most commonly bilateral vasogenic edema.　PRES　during first trimester gestation is exceptional and in our report mimicking CNS tumor. An　18-year-old　G1P0　Hispanic woman　was admitted with　headache, left-sided　hemiparesis and left-sided visual loss for 4 days. Exam was consistent for drowsiness, dysarthria,　left homonymous hemianopia, left facial droop and left hemiplegia with left hemi-sensory loss. By pelvic ultrasound she had a single 9-week intrauterine pregnancy with no detectable fetal heart tone. MRI brain: large area of increased T2 signal in the right parietal occipital and upper temporal and posterior right frontal lobe white matter with mass effect of 6mm midline shift and no evidence of hemorrhage. There was high suspicion for a glial neoplasm. MRA of head and neck　and EEG　were unremarkable. IR cerebral angiogram had no evidence of vascular abnormalities. Eventual MR spectroscopy, choline/NAA ratio was　(&lt; 2/1), elevated lactate/fat　peak suggestive of inflammatory versus infectious process. She had D&C for missed abortion and pathology was negative for malignancy.　Further brain biopsy on day 5 demonstrated reactive astrogliosis with microglial activation, scattered macrophages with white matter vacuolation. Biopsy specimen was negative for infections. TPO Ab, NMO/AQP4, Ttg IgA and rheumatologic panel were negative. The pathology was most compatible with PRES. Repeat MRI had decreasing mass effect and　increased patchy subcortical restricted diffusion in the right occipital and temporo-parietal lobes. She had inpatient rehabilitation leading to complete recovery.
NIMG-69. PERSONALIZED CONNECTOMIC SIGNATURES: BRIDGING THE GAP BETWEEN NEURO-ONCOLOGY AND CONNECTOMICS
Authors: Osmanlioglu Yusuf , Parker Drew , Brem Steven , Shokoufandeh Ali , Verma Ragini 
Published: December 2020

Abstract

PURPOSE
Connectomics has led to significant neuroscientific findings within the last two decades, eventually making impact in the clinics. Neuro-oncology can benefit immensely from connectomics in evaluating structural connectivity of brains with tumor for pre- and post-treatment planning, as a tumor connectome along with derived network measures will make it possible to determine the cognitive effects of treatment and quantify the effect of surgery on quality of life. However, generating connectomes in the presence of tumor is a challenging task. Specifically, registration of an atlas to the brain, which is essential in parcellating the brain into regions of interest, fails around the tumor due to mass effect and infiltration related distortions which are not present in the atlas that comes from a healthy brain. We aim to tackle this problem by introducing a novel atlas registration method.

METHOD
Although tumor deforms the geometrical shape of its surrounding regions, it does not violate the connectivity of displaced cortical voxels to the rest of the brain. Leveraging this fact, we represent the brain as an annotated graph with nodes representing ROIs encoding geometric features of regions and weighted edges representing the connectivity between regions. In encoding the surroundings of the tumor into the graph, we subsample the region into smaller patches to represent the area with multiple nodes. We then calculate many-to-one graph matching between the graphs of a tumor patient and a healthy control to associate surroundings of tumor with healthy ROIs.

OUTCOME
A tumor connectome showing how the connectivity is morphed around the tumor, which can further be extended to creating connectomes of recurrence. CLINICAL

IMPLICATIONS
Use of connectomes can revolutionize neuro-oncology by helping surgeons in estimating structural, functional, and behavioral outcomes of resection prior to surgery and in predicting recovery after the surgery, potentially suggesting subject specific treatment plans.