bluuebunny/crossref_metadata_2025 huggingface dataset:
NCOG-65. MR-GUIDED LASER INTERSTITIAL THERMAL THERAPY FOR BRAIN TUMORS IN GERIATRIC PATIENTS
Authors: Ginalis Elizabeth , Danish Shabbar
Published: December 2020

INTRODUCTION

There is a paucity of studies assessing the use of magnetic resonance-guided laser interstitial thermal therapy (LITT) in the elderly population.

METHODS

Geriatric patients (≥65 years) treated with LITT for intracranial tumors at a single institution from January 2011 to November 2019 were retrospectively identified. We grouped patients into two cohorts: 65-74 years (group 1) and 75 years or older (group 2). Baseline characteristics, operative parameters, postoperative course, and morbidity were recorded.

RESULTS

There were 55 patients who underwent 64 distinct LITT procedures. The majority of tumors (62.5%) treated were recurrent brain metastasis/radiation necrosis. The median hospital length of stay was 1 day, with no significant difference between age groups. Hospital stay was significantly longer in patients who presented with a neurological symptom and in those who experienced a postoperative complication. The majority of patients (68.3%) were discharged to their preoperative accommodation. Rate of discharge to home was not significantly different between age groups. Those discharged to rehabilitation facilities were more likely to have presented with a neurological symptom. Nine patients (14.1%) were found to have acute neurological complications, with nearly all patients showing complete or partial recovery at follow-up. The 30-day postoperative mortality rate was 1.6% (n = 1). The complication and 30-day postoperative mortality rate were not significantly different between age groups.

CONCLUSIONS

LITT can be considered as a minimally invasive and safe neurosurgical procedure for treatment of intracranial tumors in geriatric patients. Careful preoperative preparation and postoperative care is essential as LITT is not without risk. Appropriate patient selection for cranial surgery is essential as neurosurgeons treat an increasing number of elderly patients, but advanced age alone should not exclude patients from LITT.
NCOG-66. IMPLICATION OF D-DIMER IN THE DETECTION OF DEEP VENOUS THROMBOSIS (DVT) /PULMONARY EMBOLISM (PE) IN HIGH GRADE GLIOMA PATIENTS WITHOUT CLASSIC SYMPTOMS OF DVT/PE ON OR OFF AVASTIN TREATMENT
Authors: Jha Ruchika , Ranjan Tulika , Yu Alexander , Wegner Rodney , Karlovits Stephen
Published: December 2020

The incidence of DVT/PE in high grade glioma patients is very high with increased risk of intracranial hemorrhage (ICH) in patients with recent surgery, Avastin and chemotherapy induced thrombocytopenia. We have frequently encountered patients with PE who presented with increased fatigue and somnolence before they developed classic symptoms of PE. It is critical that a high index of suspicion be maintained and patient screened for early detection of PE. A retrospective chart review from June 2015 to May 2020 is being performed on 500 patients with high grade glioma. D-Dimer was used as a screening test for early detection of DVT/PE. Of the 175 patients analyzed 57(32.5 %) patients had DVT/PE, 12 had DVT only and 45 patients had PE with or without DVT. Fatigue which was out of proportion to the expected chemotherapy/radiation side effects was present in 38/45 patients with PE. Classic symptoms of PE were only seen in 10/45 patients. Of 57 patients with DVT/PE with positive D-Dimer 10 asymptomatic patients were on Avastin at the time of diagnosis. The median D Dimer value for 44 positive patients was 2.43 (0.57-23.95).Of the 57 positive patients 52 (91.2%) were treated with full anticoagulation- lovenox (n-35), coumadin (n-8), eliquis (n-7) and xeralto (n-2). The IVC filter was placed in 6 patients.High risk patients were fully anticoagulated for 1-3 months. Patients with resolution of PE/DVT were switched to preventive dose of anticoagulants. Two patients had h/o hypercoagulable disorder. Two patients had symptomatic ICH on lovenox and 1 had asymptomatic sub centimeter ICH on Xeralto. Conclusion- D Dimer is very helpful in the early detection of DVT/PE in high grade glioma patients. Patients with excessive Fatigue and somnolence can be screened for PE using D-Dimer.The D Dimer screening can help with early detection of DVT/PE in patients being treated with Avastin.
NCOG-71. GENOME ASSOCIATIONS WITH NEUROCOGNITIVE OUTCOMES, CEREBRAL MICROBLEEDS (CMBS), AND BRAIN VOLUME AND WHITE MATTER (WM) CHANGES IN PEDIATRIC BRAIN TUMOR SURVIVORS
Authors: Kline Cassie , Stoller Schuyler , Byer Lennox , Edwards Caleb , Prasad Rachna , Torkildson Joseph , Gauvain Karen , Samuel David , Lupo Janine , Morrison Melanie , Tong Elizabeth , Savchuk Solomiia , Valencia Christian Rodrigo Ugaz , Rauschecker Andreas , Rudie Jeffrey , Hoffmann Thomas , Dubal Dena , Fullerton Heather , Mueller Sabine
Published: December 2020

OBJECTIVE

To identify genetic predictors of neurocognition, CMBs, brain volume, and WM changes in pediatric brain tumor survivors.

METHODS

Patients were selected from an existing cohort (RadART) if they had: 1) at least one neurocognitive evaluation using computer-based CogState; 2) available DNA; 3) standard imaging. Candidate gene or genome-wide genotyping was performed on all patients. CMBs were identified using a semi-automated algorithm developed in MATLAB. Volume of T2/FLAIR WM signal abnormality was measured using a semi-automated method based on a convolutional neural network. Brain volume and cortical thickness were measured using FreeSurfer volumetric analysis. Logistic and linear regression were done to compare phenotypes with candidate genotypes. Genome-wide efficient mixed-model analysis was done to compare neurocognition and CMBs. Gene set analysis was done using https://fuma.ctglab.nl/.

RESULTS

APOE4 was a candidate variant associated with non-lobar, larger volume CMBs (p< 0.05). At the GWAS-level (n=225), specific genes trended with visual memory, psychomotor function, and CMB count (p< 5x10-8). Using gene set analyses, there were gene set trends seen with CMB count and psychomotor function. Small sample size and low mutant allele frequency limited reliability of these findings. Preliminary volumetric analysis show reduced volume within the right parietal, medial occipital and inferior temporal lobes with increased cortical thickness in the left occipital and medial parietal lobe in patients carrying the ApoE4 allele. WM signal assessments are ongoing.

CONCLUSION

Genetic markers may be associated with neurocognition, CMBs, brain volume and WM changes in pediatric brain tumor survivors; however, larger cohorts are needed to confirm specific gene relevance.
NCOG-76. BASELINE COGNITIVE ASSESSMENT IN GLIOMA PATIENTS WITH MGMT PROMOTOR METHYLATION AND/OR 1p19q CODELETION
Authors: Park Sydney , Giles Abigail , Liberatore Grace , Morgan Katherine , DeBruhl Cynthia , Hsu Fang-Chi , Cramer Christina , Strowd Roy , Chan Michael , Lesser Glenn , Laxton Adrian , Tatter Stephen , Cummings Tiffany
Published: December 2020

INTRODUCTION

Methylguanine methyltransferase (MGMT) methylation status is associated with better overall survival while 1p19q co-deletion is associated with long-term survival. Cognitive dysfunction is a common complication of brain tumors and treatment; however, information regarding the relationship between MGMT status, 1p19q codeletion, and cognition is limited.

METHOD

Baseline neuropsychological testing was performed in patients with malignant glioma prior to radiation and/or chemotherapy administration. A retrospective data analysis was conducted. We calculated composite and subdomain scores for attention/executive functioning, memory, and language in patients with or without MGMT promotor methylation and/or 1p19q codeletion.

RESULTS

Thirty-eight patients (Age M = 48.73 ± 14.98; 50% female) diagnosed with glioma (29% grade II, 16% grade III, 21% grade IV; Karnofsky Performance Status score (KPS) M = 88.75 ± 14.24) were selected from a retrospective. Memory was marginally significant, such that methylated participants performed better on memory tasks than the unmethylated group (p = .053). Independent samples t-test revealed no significant differences between either marker across the overall cognitive composite (methylated M = 41.35; unmethylated: M = 39.91; p = .955; 1p19q co-deleted: M = 50.94; 1p19q intact: M = 43.66; p = .158) and subdomains attention/executive functioning (p = .585; p = .157) and language (p = .581; p = .765). Logistic regression showed MGMT does not predict cognitive status (p =.052) and there were not enough cases to complete the model with 1p19q.

CONCLUSION

MGMT status may be correlated with baseline cognitive status as MGMT methylated patients had better memory scores than their unmethylated counterparts. We did not find any significant association between the remaining cognitive domains and MGMT or 1p19q although sample size is a significant limitation. These results suggest further assessment of changes in cognition during treatment through serial neuropsychological testing of glioma populations with defined marker status is warranted.
NIMG-06. GUILLAIN BARRE MIMICKING LEPTOMENINGEAL SPREAD IN CANCER PATIENTS: REPORT OF TWO CASES AN REVIEW OF LITERATURE
Authors: Benouaich-Amiel Alexandra , Yariv Orly , Goldvaser Hadar , Khasminsky Vadim , Cogan Elena , Siegal Tali , Yust-Katz And Shlomit
Published: December 2020

BACKGROUND

Guillain-Barre syndrome (GBS) is an immune acute polyradiculoneuropathy usually presented as an ascending peripheral paresis with absent tendon reflex and albumino-cytologic dissociation on cerebrospinal fluid (CSF) exam.We describe two oncologic patients with GBS who presented with atypical symptoms.

RESULTS

The first patient was a 35 years old woman with newly diagnosed grade 3 invasive breast ductal carcinoma. During the sixth courses of neo-adjuvant chemotherapy she complained at back pain and within 24 hours developed progressive severe bilateral proximal paraparesis with a D10 sensory level. Spine MRI demonstrated diffuse leptomeningeal enhancement. Since leptomeningeal spread (LMD) is uncommon at this stage of breast cancer CSF was obtained. CSF sample revealed albumin-cytologic dissociation (4 cells, protein level 340 mg/dl). EMG showed acute demyelinating neuropathy consistent with GBS. Intravenous immunoglobulins (IVIG) therapy was initiated with clinical improvement. The second patient was a 45 years old woman with newly diagnosed T-Cell lymphoma. Before initiating chemotherapy she presented with a rapidly progressive tetraparesis, hyperreflexia and cervical sensory level. Spine MRI was intact. CSF showed 22 cells without atypia, FACS negative, protein level was 74 mg/dl. The patient worsened clinically. A second CSF sample was obtained and demonstrated an albumin-cytologic dissociation (8 cells without atypia, protein level 115 mg/dl) raising the possibility of GBS. EMG showed acute axonal polyneuropathy consistent with AMSAN variant of GBS. The patient was treated with IVIG with partial recovery.

CONCLUSION

Atypical presentation of GBS could be challenging among oncologic patients and could lead to misdiagnosis and delay in treatment.
NIMG-10. A RETROSPECTIVE ANALYSIS OF SURVIVAL FOLLOWING TREATMENT WITH BEVACIZUMAB IN GLIOBLASTOMA PATIENTS WITH RADIOGRAPHICALLY-CONFIRMED SUBEPENDYMAL OR LEPTOMENINGEAL SPREAD OF DISEASE
Authors: Farooq Shama , Yildirim Onur , Young Robert , Tisnado Jamie , Miller Alexandra
Published: December 2020

OBJECTIVE

We performed a retrospective analysis examining subependymal disease (SED) and leptomeningeal disease (LMD) in bevacizumab treated IDH-wildtype glioblastoma (GBM) patients to assess potential differences in survival.

BACKGROUND

GBMs are highly infiltrative and often invade the subependymal and leptomeningeal space making them challenging to treat. At recurrence, patients are commonly treated with bevacizumab, which leads to decreased tumor size and swelling. Patients have improved PFS, but there is no benefit in OS. This may reflect infiltrative disease progression--a hallmark of late-stage disease. We hypothesized patients with CSF spread manifested by SED and LMD may have worse outcomes after bevacizumab than patients with non-disseminated disease.

METHODS

We retrospectively reviewed charts of all IDH-wildtype GBM patients who received bevacizumab in 2016. MRI scans were reviewed by experienced neuro-radiologists to characterize patients into radiographically defined groups (“0” = no LMD/no SED; “1”= no SED/LMD contact; “2”= no SED/LMD dissemination, and “3’= LMD present). Survival from initiation of bevacizumab to death for each group was compared to group “0” (with no SED/LMD). Survival outcomes were analyzed via t-tests.

RESULTS

We evaluated 87 IDH-WT GBM patients. Radiographically, patients were grouped-- “0”= 16 (18%), “1”= 33 (38%), “2”= 20 (23%), and “3”= 18 (21%). There was no difference between group “0” and any radiographically defined subgroups. Median survival for group “0”= 187 days; group “1”= 219 days; group “2”= 217 days; group “3”= 169 days.

CONCLUSION

Contrary to our hypothesis, there was no significant difference in survival from the initiation of bevacizumab in patients with SED or LMD. This may be related to the fact that these patients also typically have a high burden of parenchymal disease. Further work is necessary to test this hypothesis in a larger cohort.
NIMG-18. THE CLINICAL SIGNIFICANCE OF 13N-NH3, 18F-DOPA, AND 18F-FDG PET/CT IN THE DIFFERENTIAL DIAGNOSIS BETWEEN GLIOMA RECURRENCE AND TREATMENT EFFECTS
Authors: Li Cong , Yi Chang , Chen Yingshen , Xi Shaoyan , Guo Cheng-Cheng , Zhang Xiangsong , Chen Zhongping
Published: December 2020

BACKGROUND

Glioma often recurs and the imaging evaluation whether the tumor has returned after glioma treatment is still challenging. PET/CT is one of the most important techniques to assess the post-treatment of glioma. However, differentiating tumor recurrence (TuR) from treatment effects (TrE) remains difficult. In this study, we aim to retrospectively compare the diagnostic performance of three PET tracers 13N-NH3, 18F-DOPA, and 18F-FDG on PET/CT in differentiating between TuR and TrE in post-treatment glioma patients.

METHODS

Forty-three patients with MRI-suspected recurrent glioma were included. The maximum and mean standardized uptake value (SUVmax and SUVmean) of the lesion and the lesion-to-normal Gray-matter cortex uptake (L/G) ratio were recorded and the reference standard was verified by surgical histopathology or more than 6 months of follow-up with clinical/radiological. The diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis.

RESULTS

34 patients were confirmed as glioma TuR and 9 patients met the standard of TrE. The median time interval from primary diagnosis surgery to PET/CT was 14.83 months (range, 4.10-62.77 months). The SUVmax of 13N-NH3 and 18F-DOPA PET/CT at the lesions was significantly higher than normal brain tissue (13N-NH3 0.696±0.095 vs 0.486±0.071, 18F-DOPA 0.455±0.079 vs 0.194±0.031, both P< 0.001), while 18F-FDG was not (6.918±0.525 vs 6.356±0.510, P=0.290). TuR showed significantly higher L/G ratios than TrE both in 13N-NH3 and 18F-DOPA PET/CT (13N-NH3, 1.573±0.099 vs 1.025±0.128, P=0.008; 18F-DOPA, 2.729±0.131 vs 1.514±0.141, P< 0.001). The sensitivity, specificity and the area under the curve (AUC) by ROC analysis were 57.7, 100% and 0.803 for 13N-NH3, and 84.6, 100% and 0.938 for 18F-DOPA respectively.

CONCLUSIONS

PET/CT is a powerful tool to distinguish glioma TuR from TrE, and 18F-DOPA PET/CT has remarkably better differential diagnosis efficacy than 13N-NH3 and 18F-FDG.
NIMG-19. USING FUNCTIONAL ULTRASOUND (FUS) TO MAP BRAIN FUNCTIONALITY AND TUMOR VASCULATURE WITH MICROMETER-MILLISECOND PRECISION
Authors: Soloukey Sadaf , Vincent Arnaud J P E , Satoer Djaina D , Mastik Frits , Smits Marion , Dirven Clemens M F , Strydis Christos , van der Steen Antonius F W , Bosch Johannes G , De Zeeuw Chris I , Koekkoek Sebastiaan K E , Kruizinga Pieter
Published: December 2020

OBJECTIVE

In the early 20th century, Dr. Cushing first demonstrated the use of electrical stimulation mapping (ESM) to define motor and sensory cortices during neurosurgical procedures. Essentially, little has changed in what guides a neurosurgeon’s intra-operative decision-making since. Inherent limitations of ESM such as limited depth penetration and risk of seizure elicitation, warrant the development of new image-guided resection tools. Here, we present functional Ultrasound (fUS)-imaging as a new, high-resolution tool to guide intra-operative decision-making during awake tumor removal.

METHODS

fUS relies on high-frame-rate ultrasound, which offers images at thousands of frames-per-second. As such, fUS is sensitive to very small motions caused by vascular dynamics (µDoppler), allowing measurements of changes in cerebral blood volume (CBV). This facilitates the possibility to 1) detect functional response, as CBV-changes reflect changes in metabolism of activated neurons through neurovascular coupling and 2) visualize high-resolution vascular morphology of tumor and healthy tissue. During conventional awake craniotomy surgery, n= 10 patients were asked to perform 60s functional tasks to elicit cortical responses. Simultaneously, a conventional 5 MHz ultrasound probe connected to an experimental acquisition system, was placed over ESM-defined functional areas. After image acquisition, correlation analyses with the corresponding tasks revealed functional and non-functional areas. In addition, 3D vascular maps were reconstructed from subsequent 2D-Power Doppler Images (PDIs).

RESULTS

fUS was able to detect functional areas as activated using conventional motor tasks, as well as complex language-related tasks. In addition, both 2D-PDIs and 3D-reconstructions revealed the ability of fUS to detect unique high-resolution onco-vascular characteristics in high- and low-grade malignancies. In all cases, images were acquired with micrometer-millisecond (300 µm, 1.5-2.0 msec) precision at imaging depths > 5 cm.

CONCLUSIONS

Applying fUS-imaging successfully in this awake craniotomy series serves as a clear demonstration of the technique’s revolutionary potential for maximizing safe tumor removal.
NIMG-24. GLYCINE AND GLUTAMINE BY MR SPECTROSCOPY ARE IMAGING BIOMARKERS OF GLIOMA AGGRESSIVENESS
Authors: Choi Changho , Askari Pegah , Daoud Elena , Hatanpaa Kimmo , Raisanen Jack , Lewis Cheryl , Levy Michael , Patel Toral , Pan Edward , Mickey Bruce , Maher Elizabeth
Published: December 2020

Cancers reprogram their metabolism and the resulting alterations in metabolite concentrations may be closely related to the clinical behavior of the tumors. We evaluated glycine, glutamine and 2-hydroxyglutarate (2HG) in 16 adult subjects with glioblastomas (9 male and 7 female; age 43-64 years, median 58) noninvasively using proton magnetic resonance spectroscopy and examined their association with the cell proliferation rate (MIB-1 labeling index) and overall survival. MRS was acquired using point-resolved spectroscopy (PRESS TE 97ms) at 3T. Metabolite levels were quantified with reference to water. The concentrations of glycine and glutamine were both positively correlated with MIB-1 (p=.002 and .0008 respectively). The sum of glycine and glutamine levels showed stronger association with MIB-1 (p< .0001). In the Kaplan-Meier overall survival analysis, the median survival was significantly shorter in patients with glycine levels higher than 2.3 mM than those with concentrations less than 2.3 mM. For glutamine, the patients with higher than 5.7 mM showed association with poor survival. The log-rank p value was substantially smaller in glutamine compared to glycine (p=.008 vs .04). The sum of glycine and glutamine levels showed stronger association with overall survival. 2HG level greater than 1 mM was associated with long survival, which was as expected since elevation of 2HG represents IDH mutant tumors and IDH mutation carries favorable prognosis. Given the association of low 2HG with poor survival, we tested metabolic ratios to 2HG, in which 2HG estimates < 1 mM were put as 1 mM. The glycine/2HG, glutamine/2HG, and (glycine+glutamine)/2HG showed stronger association with overall survival, compared to glycine, glutamine, and glycine+glutamine. Our data suggested that increased metabolism of glycine and glutamine is closely associated with rapid cell proliferation and poor clinical outcome, suggesting the metabolites as an MRS imaging biomarker of glioma aggressiveness.
NIMG-29. DEVELOPING AUTOMATIC SEGMENTATION METHOD FOR BRAIN TUMOR MR IMAGES THAT CAN BE USED AT MULTIPLE FACILITIES
Authors: Takahashi Satoshi , Takahashi Masamichi , Kinoshita Manabu , Miyake Mototaka , Kawaguchi Risa , Shinojima Naoki , Mukasa Akitake , Saito Kuniaki , Nagane Motoo , Otani Ryohei , Ueki Keisuke , Tanaka Shota , Hata Nobuhiro , Nishikawa Ryo , Arita Hideyuki , Nonaka Masahiro , Tamura Kaoru , Tateishi Kensuke , Uda Takehiro , Fukai Junya , Okita Yoshiko , Tsuyuguchi Naohiro , Kanemura Yonehiro , Kobayashi Kazuma , Sese Jun , Ichimura Kouichi , Narita Yoshitaka , Hamamoto Ryuji
Published: December 2020

BACKGROUND

Manual segmentation of brain tumor images from a large volume of MR images generated in clinical routines is difficult and time-consuming. Hence, it is imperative to develop a machine learning model for automated segmentation of brain tumor images.

PURPOSE

Machine learning models for automated MR image segmentation of gliomas may be useful. However, the image differences among facilities cause performance degradation and impede successful automatic segmentation. In this study, we proposed a method to solve this issue.

METHODS

We used the data from the Multimodal Brain Tumor Image Segmentation Benchmark (BraTS) and the Japanese cohort (JC) datasets collected from 10 facilities. Three models for tumor segmentation were developed. The BraTS model was trained on the BraTS dataset, and the JC model was trained on the JC dataset; whereas, the Fine-tuning model was a fine-tuned BraTS model using the JC dataset.

RESULTS

MR images of 544 patients were obtained for the JC dataset. Half of the JC dataset was used for independent testing. The Dice coefficient score of the JC model for the JC dataset was 0.779± 0.137, whereas that of the BraTS model was remarkably lower (0.717 ± 0.207). The mean of the Fine-tuning models for the JC dataset was 0.769 ± 0.138. There was a significant difference between the BraTS and JC models (P < 0.0001) and the BraTS and Fine-tuning models (P = 0.002); however, no significant difference was observed between the JC and Fine-tuning models (P = 0.673).

CONCLUSIONS

Application of the BraTS model to heterogeneous datasets can significantly reduce its performance; however, fine-tuning can solve this issue. Since our fine-tuning method only requires less than 20 cases, this methodology is particularly useful for a facility where there are a few glioma cases.
NIMG-30. PET IMAGING OF ANDROGEN RECEPTOR EXPRESSION IN PATIENTS WITH GBM USING [18F]-FDHT
Authors: Mordechai Anat , Shamni Ofer , Zalcman Nomi , Moscovici Samuel , Chicheportiche Alexandre , Shoshan Yigal , Shahar Tal , Charbit Hanna , Guterman Mijal , Paldor Iddo , Mishani Eyal , Lossos Alexander , Orevi Marina , Lavon Iris
Published: December 2020

BACKGROUND

GBM is associated with poor overall survival partly due to lack of effective treatment. Recently we showed that androgen receptor (AR) protein is overexpressed in 56% of GBM specimens and that AR antagonists induced dose-dependent death in several glioblastoma cell lines. Treatment of mice implanted with human GBM with AR antagonists significantly reduced the growth of the tumor and prolonged the lifespan of the mice. 18f-fluorine-radiolabeled Dihidrotestosteron (DHT), a natural ligand of AR, [16β-18F-fluoro-5α-dihydrotestosterone ([18F]-FDHT)] is one of the PET tracers used to detect AR expression in metastatic prostate cancer. The aim of this study was to identify AR-expressing GBM tumors in real time using PET-CT scan with [18F]-FDHT.

MATERIALS AND METHODS

Twelve patients with GBM underwent a dynamic (first 30 min) and whole body static (later 60-80 min) [18F]-FDHT PET/CT (296-370 MBq) scans 2-4 days prior to the surgery or biopsy. Protein was extracted from the tumor and subjected to western blot analysis. AR Protein fold change of each tumor sample was calculated by densitometry analysis compared with that of normal brain, following normalization to GAPDH.

RESULTS

At ~60 min after injection, 6 of the 12 patients showed significantly higher tumor accumulation of [18F]-FDHT, compared to reference tissue (SUV/Control)mean: 1.33-2.63 fold, (SUV/control)max: 1.4-3.43 fold. The patient who had higher tumor accumulation of [18F]-FDHT, demonstrated also high (1.6-2.27 fold/normal brain) AR protein expression within the tumor. Pearson-correlation-coefficient analysis for the (SUV/Control)mean at ~60 min after the injection versus AR protein expression, was positive and significant (R=0.841;p=0.0024).

CONCLUSION

This study demonstrated for the first time that [18F]-FDHT PET can identify AR-positive-GBM-tumors (with sensitivity and specificity at 100%) and may therefore be a powerful tool to select patients eligible for treatment with AR antagonists. It could possibly be employed also to monitor treatment response and/or progression during the course of therapy.
NIMG-32. THE PREDICTIVE CAPACITY OF PRE-OPERATIVE IMAGING ANALYSIS IN DIFFUSE GLIOMA: A COMPARISON OF CONNECTOMICS, RADIOMICS, AND CLINICAL PREDICTIVE MODELS
Authors: Harrison Rebecca , Tan Bryce Wei Quan , Tan Hong Qi , Tan Lloyd , Lim Mei Chin , Yong Clement , Kuo John , Kesler Shelli
Published: December 2020

BACKGROUND

Radiomics and connectome analysis are distinct and non-invasive methods of deriving biologic information from MRI. Radiomics analyzes features intrinsic to the tumor, and connectomics incorporates data regarding the tumor and surrounding neural circuitry. In this study we used both techniques to predict glioma survival.

METHODS

We retrospectively identified 305 adult patients with histopathologically confirmed WHO grade II–IV gliomas who had presurgical, 3D, T1-weighted brain MRI. Available clinical variables included tumor lobe, hemisphere, multifocal nature grade, histology extent of surgical resection, patient age gender. For connectomics, we calculated nodal efficiencies, network size and degree for all pairs of 33 voxel cubes spanning the entire gray matter volume using similarity-based extraction and graph theory. Radiomic features were extracted using Pyradiomics and subjected to patient-level and population-level clustering (N=172). These clusters were then used to construct a multi-regional spatial interaction matrix for model building. Cox proportional hazards models were fit for clinical variables alone, connectomics alone, radiomics alone, connectomics+clinical and radiomics+clinical. We implemented 10-folds cross-validation and examined the mean area under the curve (AUC) across validation loops.

RESULTS

Median survival time was 134.2 months. The mean AUC for the clinical model was 0.79 +/- 0.01, the connectome model was 0.88 +/- 0.01, the combined connectome + clinical model was 0.93 +/- 0.01, the radiomic model was 0.64 +/- 0.05 and the radiomics+clinical model was 0.89+/-0.03. Radiomic analysis of the entire dataset as well as comparisons of radiomic+connectomics +/- clinical models are pending.

CONCLUSIONS

The combination of clinical variables and connectome analysis provided a more robust predictive model than other models. This suggests that connectome analysis incorporates valuable clinically-predictive information which can augment our capacity for prognostication of patients with diffuse glioma. These methods warrant further evaluation in larger prospective study of patients with diffuse glioma.
NIMG-41. VARIATION IN PERFUSION AND PERMEABILITY MRI DEPENDING ON VASCULAR INPUT FUNCTION SELECTION
Authors: Abbasian Parandoush , Ryner Lawrence , Shankar Jai , Essig Marco , Pitz Marshall
Published: December 2020

BACKGROUND

According to the updated RANO criteria, MRI contrast enhancement and peritumoral edema during the initial 12 weeks within the radiation field following chemoradiation may be pseudoprogression (PP) or true progression (TP). This ambiguity results in diagnostic uncertainty and delays in effective therapies. MRI perfusion and permeability imaging markers, including relative blood volume (rBV), and volume transfer constant (Ktrans), may be useful in differentiating PP from TP. Both techniques rely on identification of a vascular input function (VIF) to produce reliable output maps.

METHODS

Perfusion and permeability maps were acquired from 7 patients on a Siemens 3T Verio MRI as part of an ongoing prospective study on glioblastoma multiforme. Patients received standard surgical resection with concurrent chemo-radiotherapy treatment and MRI follow-up at one and every 2 months. Maps were based on the follow-up MRI. The 3D contrast enhancing lesion (CEL) was segmented from the T1-Post-Gd MRI. VIF pixels were identified in the internal carotid artery (ICA), the M2 segment of the middle cerebral artery (MCA2), the superior sagittal sinus (SSS), automatically using software (Olea Sphere 3.0.22), and auto-edited (removed pixels from the auto VIF definition that were outside the brain).

RESULTS

For the different VIF pixel selections (ICA, MCA2, SSS, Auto, Auto-edited), mean Ktrans values from CEL were 0.32, 0.48, 0.05, 0.09, 0.08, respectively, showing a 10-fold variation. Mean rBV values from CEL were 2.70, 2.36, N/A, 3.10, 3.19, respectively, showing a 1.3-fold variation.

CONCLUSIONS

VIF pixel selection is a critical step in generating reliable perfusion and permeability MRI maps. Variation of up to a factor of 10 in the Ktrans values, depending on VIF selection, was observed. SSS for the permeability VIF resulted in maps that most closely matched literature values, whereas perfusion imaging showed less sensitivity to VIF selection.
NIMG-42. HOROS SOFTWARE FOR POSTOPERATIVE ANALYSIS OF PEDIATRIC HIGH-GRADE GLIOMAS
Authors: Elsawaf Yasmeen , Anetsberger Stephanie , Aguilar-Bonilla Ana , Smith Amy , Elbabaa Samer
Published: December 2020

INTRODUCTION

Horos (LGPL 3.0) is a free, open source medical image viewer that has gained attention in the neurosurgical community because of the familiar OsiriX-based interface and its useful three-dimensional (3D) volumetric rendering capabilities. We present the use of Horos software as a postoperative tool for residual tumor volume analysis in children with high-grade gliomas.

METHODS

A retrospective study of 11 pediatric patients with histologically confirmed HGG underwent tumor resection (n=8) or biopsy (n=3) as definitive treatment from 6/2011 to 6/2019. Volumetric data and extent of resection were obtained via region of interest-based 3D analysis using Horos image-processing software. Age, initial tumor volume, extent of resection, and postoperative residual volume were assessed as predictors of overall survival or event free survival.

TECHNIQUE

Region of interest (ROI) segmentation was performed utilizing the “Closed Polygon Tool” to outline the tumor and the “Generate Missing ROIs” function to capture the entirety of the tumor within the MRI series. The “Computer Volume” function was used to render the 3D tumor volumes. The preoperative and postoperative tumor volumes were compared per patient to yield the percent extent of resection and residual volume.

RESULTS

The Horos software is a highly effective means of volumetric analysis for high-grade gliomas depicted in T1 and T2 MRI series. In our series, eight (73%) patients underwent tumor resection and three (27%) underwent biopsy. Patients who underwent resection were older than biopsy patients [12 (8-18) vs. 9 (8-21) years old]. Age, initial tumor volume, extent of resection, and postoperative residual volume were not significant predictors of overall survival or event free survival.

CONCLUSION

Horos software provides increased accuracy and confidence in determining post-operative volume and is useful in assessing the impact of residual volume on outcome after maximal safe resection in pediatric patients with high-grade gliomas.
NIMG-43. IMAGING FINDINGS FOLLOWING REGORAFENIB IN PATIENTS WITH MALIGNANT GLIOMA: FET PET ADDS VALUABLE INFORMATION TO ANATOMICAL MRI
Authors: Werner Jan-Michael , Tscherpel Caroline , Stoffels Gabriele , Lohmann Philipp , Fink Gereon R , Langen Karl-Josef , Galldiks Norbert
Published: December 2020

BACKGROUND

Recent phase 2 data showed that the small molecule regorafenib with antiangiogenic properties has promising effectivity in glioblastoma patients at first progression. Following antiangiogenic therapy with bevacizumab, amino acid PET provides valuable additional diagnostic information regarding bevacizumab-related effects on MRI (e.g., pseudoresponse). In contrast, only a little is known about regorafenib. Thus, we evaluated prospectively the value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the assessment of regorafenib-related treatment effects.

METHODS

Twenty-two patients with progressive malignant glioma (median number of relapses, 2; range, 1-4) were included. Up to now, 10 of 22 patients were eligible for data evaluation and underwent regorafenib therapy (median number of cycles, 2; range, 1-5 cycles). FET PET and MRI were performed at baseline and after the second cycle. After the second cycle, MRI was performed every 8 weeks. In case of a suspicious MRI after the second cycle, a FET PET scan was added. MRI changes were evaluated according to the RANO criteria. Maximum tumor-to-brain ratios (TBRmax) were calculated. Pseudoresponse was considered if (i) the follow-up MRI showed an improvement (i.e., at least “partial response” according to RANO criteria) despite subsequent clinical progression, and (ii) an increase of TBRmax>25% occurred. Pseudoresponse was confirmed if (i) the subsequent MRI follow-up showed progression, and/or (ii) the clinical status worsened, or the patient died.

RESULTS

In 4 of 10 patients, FET PET provided clinically relevant additional information. In two patients, pseudoresponse could be confirmed. Furthermore, in one patient with stable disease according to MRI, increasing TBRmax (+138%) enabled earlier diagnosis of tumor progression (time benefit, 5 weeks). In another patient without signs of MRI response after 2 cycles, decreasing TBRmax (-23%) indicated metabolic response and was associated with a significant clinical improvement.

CONCLUSIONS

FET PET seems to add valuable diagnostic information for regorafenib therapy monitoring.
NIMG-45. DEEP LEARNING-BASED PERITUMORAL MICROSTRUCTURE MAPPING IN GLIOBLASTOMAS USING FREE WATER VOLUME FRACTION
Authors: Samani Zahra Riahi , Parker Drew , Alappatt Jacob Antony , Brem Steven , Verma Ragini
Published: December 2020

PURPOSE

Characterization of the peritumoral microenvironment is a widely researched, but as yet unsolved problem. Determining the tissue microstructure differences between tumor types, arising from differences in infiltration, edema, and disease driven changes in cellularity is important to be able to guide treatment options. Diffusion tensor imaging with characterization of extracellular free water provides unique information of the tissue microstructure. The goal of this work is to leverage this information by applying deep learning on free water maps and create a microstructure map of the peritumoral area, to aid in targeted resection, radiotherapy and treatment management in the form of a crucial supplemental radiomic feature, replacing all other diffusion derived measures.

METHOD

We leveraged the widely different peritumoral microenvironments of GBMs and Metastatic tumors to create the microstructure maps. Tumor and peritumoral regions were automatically delineated in 143 patients with brain tumors (89 glioblastomas and 54 metastasis, ages 19-87 years, 77 females), and free water maps were computed in the peritumoral regions using their DTI data. We trained a Convolutional Neural Network (CNN) on 32x32 mm patches in the peritumoral area from GBMs and Mets, labeled as non-enhancing tumor (low free-water) and edema (high free-water), respectively. An independent test set was used and the CNN associated a voxel-wise probability to their peritumoral region to produce microstructure maps of GBMs and Mets which were then statistically compared.

RESULT

For comparison, a t-test was used showing significant group difference in the microstructure map between Mets and GBMs (p< 0.05).

CONCLUSION

The voxel-wise microstructure map is able to capture the cellularity differences in the peritumoral region, based on DTI-based characterization of the tissue microstructure. CLINICAL

IMPORTANCE

The microstructure map provides a novel insight into the peritumoral microenvironment using a measure that can be derived from clinically feasible DTI data, replacing pre-existing DTI measures.
NIMG-47. METABOLIC CHARACTERIZATION OF IDH MUTANT LOWER GRADE GLIOMA USING SPECTROSCOPIC IMAGING OPTIMIZED FOR 2-HYDROXYGLUTARATE DETECTION
Authors: LaFontaine Marisa , Autry Adam , Philips Elizabeth , Jalbert Llewellyn , Villanueva-Meyer Javier , Chang Susan , Li Yan
Published: December 2020

INTRODUCTION

Mutations in isocitrate dehydrogenase (IDH1/2) genes are both diagnostic and prognostic biomarkers for lower grade gliomas, which can be noninvasively evaluated via MRS detection of 2-hydroxyglutarate (2HG). A high percentage of lower grade gliomas harbor IDH mutations that have a major impact on tumor biology.

METHODS

Forty IDH-mutant lower grade glioma patients were recruited and scanned using 2HG-optimized 97ms PRESS spectroscopy prior to surgical resection, whereupon image-guided tissue samples were acquired and analyzed via histopathology. Spectra were processed and quantified using LCModel. Wilcoxon ranksum tests were used to compare the difference in metabolic parameters between patient subgroups. Cox proportional hazard models were used to evaluate the influence of metabolic parameters on progression free survival (PFS). Pearson and Kendall Tau rank correlations were used for metabolites and histopathology parameters.

RESULTS

Levels of 2HG were quantifiable in 37/40 (92.5%) IDH+ patients, yielding a detection rate of 92.5%. A significant difference in myoinositol/total choline was found between astrocytoma and oligodendroglioma in the newly diagnosed grade II population (N=10/13, p=0.042) and also in the overall population (N=25/15, p=0.022). 2HG/creatine was the only significant prognostic indicator on PFS in newly diagnosed patients (p=0.036, HR=4.435; N=33), who had a median PFS of 1472 days [95%CI 994 1950 days] (15 censored). Significantly decreased glutamate/creatine and increased (2HG+GABA)/creatine (p< 0.0001) were found in the T2 lesion compared to those in the normal appearing white matter. At the location where the biopsy samples were taken, there was a significant relationship between 2HG/creatine and glycine/creatine (0.93±0.01; mean±SD Tau; p=0.0005) as well as 2HG/creatine and glutathione/creatine (0.96±0.02; mean±SD Tau; p=0.001) but no significance between the metabolites and pathology parameters were found.

CONCLUSIONS

The non-invasive detection of 2HG can provide clinically relevant information for patient management and our study demonstrated both the feasibility of 2HG detection and its relationship with PFS.
NIMG-52. CHARACTERIZATION OF COGNITIVE FUNCTION IN SURVIVORS OF DIFFUSE GLIOMAS USING MORPHOMETRIC CORRELATION NETWORKS (MCN)
Authors: Wang Chencai , Van Dyk Kathleen , Cho Nicholas , Raymond Catalina , Choi Justin , Salamon Noriko , Pope Whitney , Lai Albert , Cloughesy Timothy , Nghiemphu Phioanh , Ellingson Benjamin
Published: December 2020

Advanced multimodality treatments have led to improved survival and quality of life for patients with diffuse gliomas, and widespread functional reorganization has been reported to be associated with improved cognitive function. However, investigation of morphological alterations in patients with diffuse gliomas has been problematic, largely due to the tumor resection cavities. This pilot study has overcome these challenges and aims to characterize the relationship between structural plasticity and cognitive function in survivors of diffuse gliomas. High-resolution T1 weighted images were collected from 24 patients with diffuse gliomas (mean age 44.5 ± 11.5) who had completed their treatment within the previous ten years. Interregional correlations of cortical thickness were computed to establish morphometric correlation networks (MCN) for twelve cognitively impaired and twelve non-impaired glioma patients, as well as correlated with self-reported cognitive impairment. Our findings demonstrated that both cognitively impaired (σ=1.5979) and non-impaired (σ=1.3683) glioma patients have a small world architecture in disrupted morphological networks. Although the left fusiform (p=0.0409), left inferior (p=0.0209), and temporal (p=0.0173) gyri were observed to be thicker in non-impaired patients, the robustness of their morphological network was weak and easily vulnerable to pathological attacks and neurological deterioration. Furthermore, regions such as the superior temporal gyrus (p=0.0126) and rostral middle frontal gyrus (p=0.0148) were not only identified as predominant nodes in the MCN of patients but were also found to have greater gray matter thickness, which is associated with better FACT-cognitive function. Together, these results support our hypothesis that a widespread morphological network is altered in survivors of diffuse gliomas. Predominant regions obtained by topological analysis may lead to reliable imaging biomarkers that help evaluate patients’ cognition and ability to function.
NIMG-53. GLUTAMATE/GABA RATIO ON MRS IS ELEVATED IN PATIENTS WITH LOWER GRADE GLIOMAS AND SEIZURES
Authors: Rudà Roberta , Pascuzzo Riccardo , Mo Francesca , Pellerino Alessia , Barker Peter B , Bizzi Alberto , Soffietti Riccardo
Published: December 2020

BACKGROUND

There is lack of information on the role of excitatory and inhibitory neurotransmitters in the development of seizures in patients with lower grade gliomas. Increase of glutamate and downregulation of GABA have been suggested in preclinical models and human surgical samples to be associated with brain tumor-related epilepsy.

MATERIAL AND METHODS

We prospectively investigated with the use of magnetic resonance spectroscopy (MRS) the differences in the ratio of metabolites (glutamate/GABA, glutamate/creatine and GABA/creatine) in the peritumoral areas between patients with or without seizures in a series of lower grade gliomas. Tumors were classified according to WHO Classification of 2016 as follows:11 grade II IDH mutated and 1p/19q codeleted; 3 grade III IDH mutated and 1p/19q codeleted; 6 grade II IDH mutated and 1p/19q intact; 1 grade III IDH mutated and 1p/19q intact; 1 grade II IDH wild-type. Patients received surgery alone or followed by temozolomide chemotherapy according to the presence of risk factors.

RESULTS

At baseline evaluation, maximum glutamate/GABA values were significantly higher (p=0.023) in the peritumoral area of patients with seizures (1.008 ± 0.368) with respect to those without seizures (0.691 ± 0.170). No other metabolites ratio showed significant differences between the two groups. Similar results were obtained when analyzing the metabolites ratio in the examinations during the follow-up. In the cohort of patients with seizures (n.14) variations of metabolite ratios were not associated with tumor location, 1p/19q codeletion, use of AEDs, concomitant chemotherapy or seizure characteristics (type, duration, frequency).

CONCLUSIONS

The study is ongoing with the aim of analyzing further the correlations between ratio of metabolites and status of the tumor (stable vs progressive).
NIMG-58. THE EFFECT OF CELL CONFLUENCE ON THE DISTRIBUTION OF TUMOR TREATING FIELDS
Authors: Marciano Tal , Levi Shay , Bomzon Zeev
Published: December 2020

BACKGROUND

Tumor Treating Fields (TTFields) are known to exert anti-mitotic effects on cells. Numerical simulations investigating the electric field distribution within isolated cells have been reported. These studies have shown that during metaphase a uniform electric field forms within the rounded cells. This field is thought to disrupt spindle formation through alignment of the tubulin dimers with the field. Simulations also show that during cytokinesis, a non-uniform electric field forms at the furrow, leading to strong dielectrophoretic forces that further disrupt cell division. Cells in the tumor are densely packed. We used numerical simulations to investigate how the clustering of cells influences TTFields distribution.

METHODS

COMSOL was used to numerically simulate delivery of TTFields to clusters of round cells placed in a hexagonal arrangement. The influence of the distance between the cells on field distribution was investigated. The effect of pores in the cell membrane on field distribution was also investigated.

RESULTS

Placing round cells in clusters resulted in regions of highly non-uniform fields within the cells. Strong gradients in the electric field were also observed around pores placed in the membrane. Non-uniformity and gradients in the field could result in strong dielectrophoretic forces capable of disrupting key cellular structures such as the cytoskeleton and mitotic spindle, as well as cell membrane integrity.

CONCLUSIONS

The placement of cells in close proximity to one another creates gradients in the electric field, which could be associated with very strong dielectrophoretic forces that enhance the effects of TTFields on cells. Strong dielectrophoretic forces were also observed around the membrane pores. Previous studies have reported that TTFields increases membrane permeability [Chang et al Cell Death Discovery. 2018]. The strong dielectrophoretic forces in the membrane may provide a physical mechanism by which TTFields enhance membrane permeability.
NIMG-65. STUDY OF LOCAL PERTURBATION IN COMPUTATIONAL MODELLING ON TUMOR TREATING FIELDS (TTFIELDS) THERAPY
Authors: Zeevi Oshrit , Bomzon Zeev , Marciano Tal
Published: December 2020

INTRODUCTION

Tumor Treating Fields (TTFields) are an approved therapy for glioblastoma (GBM). A recent study combining post-hoc analysis of clinical trial data and extensive computational modelling demonstrated that TTFields dose at the tumor has a direct impact on patient survival (Ballo MT, et al. Int J Radiat Oncol Biol Phys, 2019). Hence, there is rationale for developing TTFields treatment planning tools that rely on numerical simulations and patient-specific computational models. To assist in the development of such tools is it important to understand how inaccuracies in the computational models influence the estimation of the TTFields dose delivered to the tumor bed. Here we analyze the effect of local perturbations in patient-specific head models on TTFields dose at the tumor bed.

METHODS

Finite element models of human heads with tumor were created. To create defects in the models, conductive spheres with varying conductivities and radii were placed into the model’s brains at different distances from the tumor. Virtual transducer arrays were placed on the models, and delivery of TTFields numerically simulated. The error in the electric field induced by the defects as a function of defect conductivity, radius, and distance to tumor was investigated.

RESULTS

Simulations showed that when a defect of radius R is placed at a distance, d >7R, the error is below 1% regardless of the defect conductivity. Further the defects induced errors in the electric field that were below 1% when σrR/d < 0.16, where σrR/d < 0.16, where σr = (σsphere – σsurrounding)/(σsphere + σsurrounding).σsurroundings is the average conductivity around the sphere and σsphere is the conductivity of the sphere.

CONCLUSIONS

This study demonstrates the limited impact of local perturbations in the model on the calculated field distribution. These results could be used as guidelines on required model accuracy for TTFields treatment planning.