Publications by authors named "Seung Hong Choi"

288 Publications

Radiological assessment schedule for 1p/19q-codeleted gliomas during the surveillance period using parametric modeling.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab069. Epub 2021 May 20.

Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: There have been no evidence-based guidelines on the optimal schedule for the radiological assessment of 1p/19q-codeleted glioma. This study aimed to recommend an appropriate radiological evaluation schedule for 1p/19q-codeleted glioma during the surveillance period through parametric modeling of the progression-free survival (PFS) curve.

Methods: A total of 234 patients with 1p/19q-codeleted glioma (137 grade II and 97 grade III) who completed regular treatment were retrospectively reviewed. The patients were stratified into each layered progression risk group by recursive partitioning analysis. A piecewise exponential model was used to standardize the PFS curves. The cutoff value of the progression rate among the remaining progression-free patients was set to 10% at each scan.

Results: Progression risk stratification resulted in 3 groups. The optimal magnetic resonance imaging (MRI) interval for patients without a residual tumor was every 91.2 weeks until 720 weeks after the end of regular treatment following the latent period for 15 weeks. For patients with a residual tumor after the completion of adjuvant radiotherapy followed by chemotherapy, the optimal MRI interval was every 37.5 weeks until week 90 and every 132.8 weeks until week 361, while it was every 33.6 weeks until week 210 and every 14.4 weeks until week 495 for patients with a residual tumor after surgery only or surgery followed by radiotherapy only.

Conclusions: The optimal radiological follow-up schedule for each progression risk stratification of 1p/19q-codeleted glioma can be established from the parametric modeling of PFS.
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http://dx.doi.org/10.1093/noajnl/vdab069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284622PMC
May 2021

Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging Assessment of Optic Pathway Function in Patients With Anterior Visual Pathway Compression.

J Neuroophthalmol 2021 Jul 13. Epub 2021 Jul 13.

Department of Radiology (KMK, SHC), Seoul National University Hospital, Jongno-gu, Republic of Korea; Department of Electrical and Computer Engineering (E-JC), Laboratory for Imaging Science and Technology, Seoul National University, Gwanak-gu, Republic of Korea; AIRS Medical (WJ), Seoul, Republic of Korea; Department of Electrical and Computer Engineering (JL), Laboratory for Imaging Science and Technology, INMC, IOER, Seoul National University, Gwanak-gu, Republic of Korea and Department of Neurosurgery (YHK), Seoul National University Hospital, Jongno-gu, Republic of Korea.

Background: In patients with sellar or parasellar tumors, it is crucial to evaluate visual field impairment in the preoperative stage and to predict visual field improvement after the surgery. The purpose of this study was to investigate the associations of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters in the optic radiations with preoperative and postoperative visual field impairment.

Methods: This prospective study included 81 participants with sellar or parasellar tumors. Multishell diffusion imaging and a visual field impairment score (VFIS) were acquired before and after the surgery. The multishell diffusion-weighted imaging was acquired to measure the neurite density and neurite orientation dispersion, as well as the diffusivity. DTI parameters were fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD). NODDI provided intracellular volume fraction (Vic), the orientation dispersion index, and isotropic volume fraction (Viso). The associations of DTI and NODDI parameters in the optic radiations with VFIS were investigated, adjusting for age, tumor height, and symptom duration.

Results: Among 162 optic radiations, 117 were functionally impaired in the preoperative stage. FA and Vic had significant negative correlations, whereas MD and RD had significant positive correlations with the VFIS (all P < 0.001). In the preoperative stage, lower FA (P = 0.001; odds ratio = 0.750) and Vic (P = 0.003; OR = 0.827) and higher MD (P = 0.007; OR = 1.244) and RD (P < 0.001; OR = 1.361) were significantly associated with the presence of visual field impairment. For the degree of postoperative improvement, preoperative lower Vic (P = 0.034; OR = 0.910) and higher MD (P = 0.037; OR = 1.103) and RD (P = 0.047; OR = 1.090) were significantly associated with more postoperative improvement.

Conclusions: DTI and NODDI parameters in the optic radiations were correlated with VFIS and associated with preoperative visual field impairments and postoperative improvement. It may help in predicting visual field improvement after the surgery in patients with sellar or parasellar tumors.
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http://dx.doi.org/10.1097/WNO.0000000000001309DOI Listing
July 2021

Prediction of Prognosis in Glioblastoma Using Radiomics Features of Dynamic Contrast-Enhanced MRI.

Korean J Radiol 2021 Jul 14. Epub 2021 Jul 14.

Department of 1Radiology, Seoul National University Hospital, Seoul, Korea.

Objective: To develop a radiomics risk score based on dynamic contrast-enhanced (DCE) MRI for prognosis prediction in patients with glioblastoma.

Materials And Methods: One hundred and fifty patients (92 male [61.3%]; mean age ± standard deviation, 60.5 ± 13.5 years) with glioblastoma who underwent preoperative MRI were enrolled in the study. Six hundred and forty-two radiomic features were extracted from volume transfer constant (K), fractional volume of vascular plasma space (V), and fractional volume of extravascular extracellular space (V) maps of DCE MRI, wherein the regions of interest were based on both T1-weighted contrast-enhancing areas and non-enhancing T2 hyperintense areas. Using feature selection algorithms, salient radiomic features were selected from the 642 features. Next, a radiomics risk score was developed using a weighted combination of the selected features in the discovery set (n = 105); the risk score was validated in the validation set (n = 45) by investigating the difference in prognosis between the "radiomics risk score" groups. Finally, multivariable Cox regression analysis for progression-free survival was performed using the radiomics risk score and clinical variables as covariates.

Results: 16 radiomic features obtained from non-enhancing T2 hyperintense areas were selected among the 642 features identified. The radiomics risk score was used to stratify high- and low-risk groups in both the discovery and validation sets (both < 0.001 by the log-rank test). The radiomics risk score and presence of isocitrate dehydrogenase (IDH) mutation showed independent associations with progression-free survival in opposite directions (hazard ratio, 3.56; = 0.004 and hazard ratio, 0.34; = 0.022, respectively).

Conclusion: We developed and validated the "radiomics risk score" from the features of DCE MRI based on non-enhancing T2 hyperintense areas for risk stratification of patients with glioblastoma. It was associated with progression-free survival independently of IDH mutation status.
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http://dx.doi.org/10.3348/kjr.2020.1433DOI Listing
July 2021

Multiparametric magnetic resonance imaging features of a canine glioblastoma model.

PLoS One 2021 9;16(7):e0254448. Epub 2021 Jul 9.

Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.

Purpose: To assess glioblastoma multiforme (GBM) formation with similar imaging characteristics to human GBM using multiparametric magnetic resonance imaging (MRI) in an orthotopic xenograft canine GBM model.

Materials And Methods: The canine GBM cell line J3T1 was subcutaneously injected into 6-week-old female BALB/c nude mice to obtain tumour fragments. Tumour fragments were implanted into adult male mongrel dog brains through surgery. Multiparametric MRI was performed with conventional MRI, diffusion-weighted imaging, and dynamic susceptibility contrast-enhanced perfusion-weighted imaging at one week and two weeks after surgery in a total of 15 surgical success cases. The presence of tumour cells, the necrotic area fraction, and the microvessel density (MVD) of the tumour on the histologic specimen were assessed. Tumour volume, diffusion, and perfusion parameters were compared at each time point using Wilcoxon signed-rank tests, and the differences between tumour and normal parenchyma were compared using unpaired t-tests. Spearman correlation analysis was performed between the imaging and histologic parameters.

Results: All animals showed a peripheral enhancing lesion on MRI and confirmed the presence of a tumour through histologic analysis (92.3%). The normalized perfusion values did not show significant decreases through at least 2 weeks after the surgery (P > 0.05). There was greater cerebral blood volume and flow in the GBM than in the normal-appearing white matter (1.46 ± 0.25 vs. 1.13 ± 0.16 and 1.30 ± 0.22 vs. 1.02 ± 0.14; P < 0.001 and P < 0.001, respectively). The MVD in the histologic specimens was correlated with the cerebral blood volume in the GBM tissue (r = 0.850, P = 0.004).

Conclusion: Our results suggest that the canine GBM model showed perfusion imaging characteristics similar to those of humans, and it might have potential as a model to assess novel technical developments for GBM treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254448PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270200PMC
July 2021

Quad-contrast Imaging: Simultaneous Acquisition of Four Contrast-weighted Images (PD-weighted, T2-weighted, PD-FLAIR and T2-FLAIR images) with Synthetic T1-weighted Image, T1-and T2-Maps.

IEEE Trans Med Imaging 2021 Jun 30;PP. Epub 2021 Jun 30.

Magnetic resonance imaging (MRI) can provide multiple contrast-weighted images using different pulse sequences and protocols. However, a long acquisition time of the images is a major challenge. To address this limitation, a new pulse sequence referred to as quad-contrast imaging is presented. The quad-contrast sequence enables the simultaneous acquisition of four contrast-weighted images (proton density (PD)-weighted, T2-weighted, PD-fluid attenuated inversion recovery (FLAIR), and T2-FLAIR), and the synthesis of T1-weighted images and T1-and T2-maps in a single scan. The scan time is less than 6 min and is further reduced to 2 min 50 s using a deep learning-based parallel imaging reconstruction. The natively acquired quad contrasts demonstrate high quality images, comparable to those from the conventional scans. The deep learning-based reconstruction successfully reconstructed highly accelerated data (acceleration factor 6), reporting smaller normalized root mean squared errors (NRMSEs) and higher structural similarities (SSIMs) than those from conventional generalized autocalibrating partially parallel acquisitions (GRAPPA)-reconstruction (mean NRMSE of 4.36% vs. 10.54% and mean SSIM of 0.990 vs. 0.953). In particular, the FLAIR contrast is natively acquired and does not suffer from lesion-like artifacts at the boundary of tissue and cerebrospinal fluid, differentiating the proposed method from synthetic imaging methods. The quad-contrast imaging method may have the potentials to be used in a clinical routine as a rapid diagnostic tool.
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http://dx.doi.org/10.1109/TMI.2021.3093617DOI Listing
June 2021

The substantial loss of H3K27me3 can stratify risk in grade 2, but not in grade 3 meningioma.

Hum Pathol 2021 Jun 26;115:96-103. Epub 2021 Jun 26.

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. Electronic address:

Trimethylation of lysine 27 of histone H3 (H3K27me3) has recently emerged as a crucial epigenetic marker in meningioma. The loss of H3K27me3 expression might predict the early recurrence of grade 1 and 2 meningiomas. However, this is controversial in terms of grade 3 meningioma and the effects of H3K27me3 on the overall survival (OS) of patients with low low-grade meningioma have not been studied. Therefore, we immunohistochemically assessed the prognostic implications of H3K27me3 expression in grade 2 and 3 meningiomas. Whole-slide H3K27me3 immunostaining was evaluated for strict quality control and to confirm a significant correlation (P < .0001) with tissue microarray results. The effects of tissue age on H3K27me3 immunostaining were also evaluated, to select an appropriate cohort for survival analysis. Log-rank tests of 115 grade 2 meningiomas and 26 grade 3 meningiomas showed that the loss of H3K27me3 expression was a prognostic factor for early recurrence (P < .0001) and death (P = .00012) in grade 2, but not in grade 3 meningioma. Multivariate analysis revealed that age, recurrent tumor, and loss of H3K27me3 expression (hazard ratio, 1.264-7.510; P = .0133) were significant for recurrentrecurrence-free survival (RFS), and that recurrent tumor and loss of H3K27me3 expression (hazard ratio, 1.717-120.621; P = .0140) were significant for OS. We concluded that H3K27me3 expression is a significant prognostic factor for the RFS and OS of patients with grade 2 meningioma; it should be considered as an ancillary test for risk stratification of this meningioma.
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http://dx.doi.org/10.1016/j.humpath.2021.06.005DOI Listing
June 2021

Contrast-enhanced MRI T1 Mapping for Quantitative Evaluation of Putative Dynamic Glymphatic Activity in the Human Brain in Sleep-Wake States.

Radiology 2021 Jun 22:203784. Epub 2021 Jun 22.

From the Departments of Radiology (S.L., R.E.Y., S.H.C., J.Y.L., I.H., K.M.K., T.J.Y., J.H.K., C.H.S.) and Clinical Pharmacology and Therapeutics (K.Y.H.), Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul 03080, Republic of Korea; Center for Nanoparticle Research, Institute for Basic Science, Seoul, Republic of Korea (S.H.C.); School of Chemical and Biological Engineering (S.H.C.) and Department of Electrical and Computer Engineering (S.J., J.L.), Seoul National University, Seoul, Republic of Korea; and Department of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin-si, Republic of Korea (S.H.O.).

Background Evaluation of the glymphatic system with intrathecal contrast material injection has limited clinical use. Purpose To investigate the feasibility of using serial intravenous contrast-enhanced T1 mapping in the quantitative evaluation of putative dynamic glymphatic activity in various brain regions and to demonstrate the effect of sleep on glymphatic activity in humans. Materials and Methods In this prospective study from May 2019 to February 2020, 25 healthy participants (mean age, 25 years ± 2 [standard deviation]; 15 men) underwent two cycles of MRI (day and night cycles). For each cycle, T1 maps were acquired at baseline and 0.5, 1, 1.5, 2, and 12 hours after intravenous contrast material injection. For the night cycle, participants had a normal night of sleep between 2 and 12 hours. The time () to reach the minimum T1 value (T1), the absolute difference between baseline T1 and T1 (peak ΔT1), and the slope between two measurements at 2 and 12 hours (slope) were determined from T1 value-time curves in cerebral gray matter (GM), cerebral white matter (WM), cerebellar GM, cerebellar WM, and putamen. Mixed-model analysis of variance (ANOVA), Friedman test, and repeated-measures ANOVA were used to assess the effect of sleep on slope and to compare and peak ΔT1 among different regions. Results The slope increased from the day to night cycles in cerebral GM, cerebellar GM, and putamen (geometric mean ratio [night/day] = 1.4 [95% CI: 1.2, 1.7], 1.3 [95% CI: 1.1, 1.4], and 2.4 [95% CI: 1.6, 3.6], respectively; = .001, < .001, and < .001, respectively). Median values were 0.5 hour in cerebral and cerebellar GM and putamen for both cycles. Cerebellar GM had the highest mean peak ΔT1, followed by cerebral GM and putamen in both day (159 msec ± 6, 99 msec ± 4, and 62 msec ± 5, respectively) and night (152 msec ± 6, 104 msec ± 6, and 58 msec ± 4, respectively) cycles. Conclusion Clearance of a gadolinium-based contrast agent was greater after sleep compared with daytime wakefulness. These results suggest that sleep was associated with greater glymphatic clearance compared with wakefulness. © RSNA, 2021 . See also the editorial by Anzai and Minoshima in this issue.
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http://dx.doi.org/10.1148/radiol.2021203784DOI Listing
June 2021

Prediction of brain age from routine T2-weighted spin-echo brain magnetic resonance images with a deep convolutional neural network.

Neurobiol Aging 2021 Apr 28;105:78-85. Epub 2021 Apr 28.

Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address:

Our study investigated the feasibility and clinical relevance of brain age prediction using axial T2-weighted images (T2-WIs) with a deep convolutional neural network (CNN) algorithm. The CNN model was trained by 1,530 scans in our institution. The performance was evaluated by the mean absolute error (MAE) between the predicted brain age and the chronological age based on an internal test set (n=270) and an external test set (n=560). The ensemble CNN model showed an MAE of 4.22 years in the internal test set and 9.96 years in the external test set. Participants with grade 2-3 white matter hyperintensity (WMH) showed a higher corrected predicted age difference (PAD) than grade 0 WMH (posthoc p<0.001). Participants diagnosed with diabetes mellitus also had a higher corrected PAD than those without diabetes (adjusted p=0.048), although it showed no significant differences according to the diagnosis of hypertension or dyslipidemia. We suggest that routine clinical T2-WIs are feasible to predict brain age, and it might be clinically relevant according to the WMH grade and the presence of diabetes mellitus.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.04.015DOI Listing
April 2021

Differentiation between glioblastoma and primary CNS lymphoma: application of DCE-MRI parameters based on arterial input function obtained from DSC-MRI.

Eur Radiol 2021 May 18. Epub 2021 May 18.

Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objective: This study aimed to evaluate whether arterial input functions (AIFs) obtained from dynamic susceptibility contrast (DSC)-MRI (AIF) improve the reliability and diagnostic accuracy of dynamic contrast-enhanced (DCE)-derived pharmacokinetic (PK) parameters for differentiating glioblastoma from primary CNS lymphoma (PCNSL) compared with AIFs derived from DCE-MRI (AIF).

Methods: This retrospective study included 172 patients with glioblastoma (n = 147) and PCNSL (n = 25). All patients had undergone preoperative DSC- and DCE-MRI. The volume transfer constant (K), volume of the vascular plasma space (v), and volume of the extravascular extracellular space (v) were acquired using AIF and AIF. The relative cerebral blood volume (rCBV) was obtained from DSC-MRI. Intraclass correlation coefficients (ICC) and ROC curves were used to assess the reliability and diagnostic accuracy of individual parameters.

Results: The mean K, v, and v values revealed better ICCs with AIF than with AIF (K, 0.911 vs 0.355; v, 0.766 vs 0.503; v, 0.758 vs 0.657, respectively). For differentiating all glioblastomas from PCNSL, the mean rCBV (AUC = 0.856) was more accurate than the AIF-driven mean K, which had the largest AUC (0.711) among the DCE-derived parameters (p = 0.02). However, for glioblastomas with low rCBV (≤ 75th percentile of PCNSL; n = 30), the AIF-driven mean K and v were more accurate than rCBV (AUC: K, 0.807 vs rCBV, 0.515, p = 0.004; v, 0.715 vs rCBV, p = 0.045).

Conclusion: DCE-derived PK parameters using the AIF showed improved reliability and diagnostic accuracy for differentiating glioblastoma with low rCBV from PCNSL.

Key Points: • An accurate differential diagnosis of glioblastoma and PCNSL is crucial because of different therapeutic strategies. • In contrast to the rCBV from DSC-MRI, another perfusion imaging technique, the DCE parameters for the differential diagnosis have been limited because of the low reliability of AIFs from DCE-MRI. • When we analyzed DCE-MRI data using AIFs from DSC-MRI (AIF), AIF-driven DCE parameters showed improved reliability and better diagnostic accuracy than rCBV for differentiating glioblastoma with low rCBV from PCNSL.
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http://dx.doi.org/10.1007/s00330-021-08044-zDOI Listing
May 2021

Prognostic Prediction Based on Dynamic Contrast-Enhanced MRI and Dynamic Susceptibility Contrast-Enhanced MRI Parameters from Non-Enhancing, T2-High-Signal-Intensity Lesions in Patients with Glioblastoma.

Korean J Radiol 2021 Aug 4;22(8):1369-1378. Epub 2021 May 4.

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Objective: Few attempts have been made to investigate the prognostic value of dynamic contrast-enhanced (DCE) MRI or dynamic susceptibility contrast (DSC) MRI of non-enhancing, T2-high-signal-intensity (T2-HSI) lesions of glioblastoma multiforme (GBM) in newly diagnosed patients. This study aimed to investigate the prognostic values of DCE MRI and DSC MRI parameters from non-enhancing, T2-HSI lesions of GBM.

Materials And Methods: A total of 76 patients with GBM who underwent preoperative DCE MRI and DSC MRI and standard treatment were retrospectively included. Six months after surgery, the patients were categorized into early progression (n = 15) and non-early progression (n = 61) groups. We extracted and analyzed the permeability and perfusion parameters of both modalities for the non-enhancing, T2-HSI lesions of the tumors. The optimal percentiles of the respective parameters obtained from cumulative histograms were determined using receiver operating characteristic (ROC) curve and univariable Cox regression analyses. The results were compared using multivariable Cox proportional hazards regression analysis of progression-free survival.

Results: The 95th percentile value (PV) of K, mean K, and median Ve were significant predictors of early progression as identified by the ROC curve analysis (area under the ROC curve [AUC] = 0.704, = 0.005; AUC = 0.684, = 0.021; and AUC = 0.670, = 0.0325, respectively). Univariable Cox regression analysis of the above three parametric values showed that the 95th PV of K and the mean K were significant predictors of early progression (hazard ratio [HR] = 1.06, = 0.009; HR = 1.25, = 0.017, respectively). Multivariable Cox regression analysis, which also incorporated clinical parameters, revealed that the 95th PV of K was the sole significant independent predictor of early progression (HR = 1.062, < 0.009).

Conclusion: The 95th PV of K from the non-enhancing, T2-HSI lesions of GBM is a potential prognostic marker for disease progression.
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http://dx.doi.org/10.3348/kjr.2020.1272DOI Listing
August 2021

Application of T1 Map Information Based on Synthetic MRI for Dynamic Contrast-Enhanced Imaging: A Comparison Study with the Fixed Baseline T1 Value Method.

Korean J Radiol 2021 Aug 4;22(8):1352-1368. Epub 2021 May 4.

Department of Radiology, Human Medical Imaging & Intervention Center, Seoul, Korea.

Objective: For an accurate dynamic contrast-enhanced (DCE) MRI analysis, exact baseline T1 mapping is critical. The purpose of this study was to compare the pharmacokinetic parameters of DCE MRI using synthetic MRI with those using fixed baseline T1 values.

Materials And Methods: This retrospective study included 102 patients who underwent both DCE and synthetic brain MRI. Two methods were set for the baseline T1: one using the fixed value and the other using the T1 map from synthetic MRI. The volume transfer constant (K), volume of the vascular plasma space (v), and the volume of the extravascular extracellular space (v) were compared between the two methods. The interclass correlation coefficients and the Bland-Altman method were used to assess the reliability.

Results: In normal-appearing frontal white matter (WM), the mean values of K, v, and v were significantly higher in the fixed value method than in the T1 map method. In the normal-appearing occipital WM, the mean values of v and v were significantly higher in the fixed value method. In the putamen and head of the caudate nucleus, the mean values of K, v, and v were significantly lower in the fixed value method. In addition, the T1 map method showed comparable interobserver agreements with the fixed baseline T1 value method.

Conclusion: The T1 map method using synthetic MRI may be useful for reflecting individual differences and reliable measurements in clinical applications of DCE MRI.
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http://dx.doi.org/10.3348/kjr.2020.1201DOI Listing
August 2021

Radiomics-based neural network predicts recurrence patterns in glioblastoma using dynamic susceptibility contrast-enhanced MRI.

Sci Rep 2021 May 11;11(1):9974. Epub 2021 May 11.

Seoul National University College of Medicine, Seoul, Republic of Korea.

Glioblastoma remains the most devastating brain tumor despite optimal treatment, because of the high rate of recurrence. Distant recurrence has distinct genomic alterations compared to local recurrence, which requires different treatment planning both in clinical practice and trials. To date, perfusion-weighted MRI has revealed that perfusional characteristics of tumor are associated with prognosis. However, not much research has focused on recurrence patterns in glioblastoma: namely, local and distant recurrence. Here, we propose two different neural network models to predict the recurrence patterns in glioblastoma that utilizes high-dimensional radiomic profiles based on perfusion MRI: area under the curve (AUC) (95% confidence interval), 0.969 (0.903-1.000) for local recurrence; 0.864 (0.726-0.976) for distant recurrence for each patient in the validation set. This creates an opportunity to provide personalized medicine in contrast to studies investigating only group differences. Moreover, interpretable deep learning identified that salient radiomic features for each recurrence pattern are related to perfusional intratumoral heterogeneity. We also demonstrated that the combined salient radiomic features, or "radiomic risk score", increased risk of recurrence/progression (hazard ratio, 1.61; p = 0.03) in multivariate Cox regression on progression-free survival.
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http://dx.doi.org/10.1038/s41598-021-89218-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113258PMC
May 2021

Localized Delivery of Theranostic Nanoparticles and High-Energy Photons using Microneedles-on-Bioelectronics.

Adv Mater 2021 Jun 6;33(24):e2100425. Epub 2021 May 6.

Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, 08826, Republic of Korea.

The low delivery efficiency of light-responsive theranostic nanoparticles (NPs) to target tumor sites, particularly to brain tumors due to the blood-brain barrier, has been a critical issue in NP-based cancer treatments. Furthermore, high-energy photons that can effectively activate theranostic NPs are hardly delivered to the target region due to the strong scattering of such photons while penetrating surrounding tissues. Here, a localized delivery method of theranostic NPs and high-energy photons to the target tumor using microneedles-on-bioelectronics is presented. Two types of microneedles and flexible bioelectronics are integrated and mounted on the edge of surgical forceps. Bioresorbable microneedles containing theranostic NPs deliver the NPs into target tumors (e.g., glioblastoma, pituitary adenoma). Magnetic resonance imaging can locate the NPs. Then, light-guiding/spreading microneedles deliver high-energy photons from bioelectronics to the NPs. The high-energy photons activate the NPs to treat tumor tissues by photodynamic therapy and chemotherapy. The controlled thermal actuation by the bioelectronics accelerates the diffusion of chemo-drugs. The proposed method is demonstrated with mouse tumor models in vivo.
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http://dx.doi.org/10.1002/adma.202100425DOI Listing
June 2021

Magnetic Resonance Imaging Parameters for Noninvasive Prediction of Epidermal Growth Factor Receptor Amplification in Isocitrate Dehydrogenase-Wild-Type Lower-Grade Gliomas: A Multicenter Study.

Neurosurgery 2021 Jul;89(2):257-265

Department of Radiology and Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, South Korea.

Background: The epidermal growth factor receptor (EGFR) amplification status of isocitrate dehydrogenase-wild-type (IDHwt) lower-grade gliomas (LGGs; grade II/III) is one of the key markers for diagnosing molecular glioblastoma. However, the association between EGFR status and imaging parameters is unclear.

Objective: To identify noninvasive imaging parameters from diffusion-weighted and dynamic susceptibility contrast imaging for predicting the EGFR amplification status of IDHwt LGGs.

Methods: A total of 86 IDHwt LGG patients with known EGFR amplification status (62 nonamplified and 24 amplified) from 3 tertiary institutions were included. Qualitative and quantitative imaging features, including histogram parameters from apparent diffusion coefficient (ADC), normalized cerebral blood volume (nCBV), and normalized cerebral blood flow (nCBF), were assessed. Univariable and multivariable logistic regression models were constructed.

Results: On multivariable analysis, multifocal/multicentric distribution (odds ratio [OR] = 11.77, P = .006), mean ADC (OR = 0.01, P = .044), 5th percentile of ADC (OR = 0.01, P = .046), and 95th percentile of nCBF (OR = 1.24, P = .031) were independent predictors of EGFR amplification. The diagnostic performance of the model with qualitative imaging parameters increased significantly when quantitative imaging parameters were added, with areas under the curves of 0.81 and 0.93, respectively (P = .004).

Conclusion: The presence of multifocal/multicentric distribution patterns, lower mean ADC, lower 5th percentile of ADC, and higher 95th percentile of nCBF may be useful imaging biomarkers for EGFR amplification in IDHwt LGGs. Moreover, quantitative imaging biomarkers may add value to qualitative imaging parameters.
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http://dx.doi.org/10.1093/neuros/nyab136DOI Listing
July 2021

Cognitive improvement effect of gintonin might be associated with blood-brain barrier permeability enhancement: dynamic contrast-enhanced MRI pilot study.

Transl Clin Pharmacol 2021 Mar 10;29(1):21-32. Epub 2021 Mar 10.

Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.

Along with the multiple neuroprotective effect, recent studies suggest that gintonin might increase the blood brain barrier permeability. We evaluated the effect of gintonin on the vascular permeability changes in different brain segments, using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). In this 8-week, randomized, open label pilot study, ten participants with subjective memory impairment but preserved cognitive function assigned to gintonin-enriched fraction (GEF) 300 mg/day or placebo groups. Korean versions of the Alzheimer's disease assessment scale (ADAS-K) and DCE-MRI parameters including K and V in different brain segments were evaluated at baseline and at 8 weeks after treatment. Nine participants completed the study protocol. No adverse events occurred during the observation period for 8 weeks in both groups. Following gintonin administration, increment trends of the brain permeability that did not reach a statistical significance were observed in the left hippocampus (K and V, both, = 0.062), left thalamus and in left putamen (K, = 0.062), and left insula and right amygdala (V, = 0.062), but not in the control placebo group. The increment of the K value in the left thalamus from the baseline was highly correlated with the change of the ADAS scores (r = -0.900, = 0.037). Gintonin might enhance the blood-brain barrier (BBB) permeability in the brain structures involved in cognitive functions. Further efficacy exploration for the synergistic effect of gintonin's BBB permeability enhancement to its other cognitive enhancing mechanisms are warranted.

Trial Registration: Clinical Research Information Service Identifier: KCT0003418.
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http://dx.doi.org/10.12793/tcp.2021.29.e2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020362PMC
March 2021

Methylation and molecular profiles of ependymoma: Influence of patient age and tumor anatomic location.

Mol Clin Oncol 2021 May 5;14(5):88. Epub 2021 Mar 5.

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Ependymomas are tumors of the central nervous system that can occur in patients of all ages. Guidelines from the World Health Organization (WHO) for the grading of ependymomas consider patient age, tumor resection range, tumor location and histopathological grade. However, recent studies have suggested that a greater focus on both tumor location and patient age in terms of transcriptomic, genetic, and epigenetic analyses may provide a more accurate assessment of clinical prognosis than the grading system proposed by WHO guidelines. The current study identified the differences and similarities in ependymoma characteristics using three different molecular analyses and methylation arrays. Primary intracranial ependymoma tissues were obtained from 13 Korean patients (9 adults and 4 children), after which whole-exome sequencing (WES), ion-proton comprehensive cancer panel (CCP) analysis, RNA sequencing, and Infinium HumanMethylation450 BeadChip array analysis was performed. Somatic mutations, copy number variations, and fusion genes were identified. It was observed that the methylation status and differentially expressed genes were significantly different according to tumor location and patient age. Several novel gene fusions and somatic mutations were identified, including a fusion mutation in a child with a good prognosis. Moreover, the methylation microarray revealed that genes associated with neurogenesis and neuron differentiation were hypermethylated in the adult group, whereas genes in the homeobox gene family were hypermethylated in the supratentorial (ST) group. The results confirmed the existence of significantly differentially expressed tumor-specific genes based on tumor location and patient age. These results provided valuable insight into the epigenetic and genetic profiles of intracranial ependymomas and uncovered potential strategies for the identification of location- and age-based ependymoma-related prognostic factors.
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http://dx.doi.org/10.3892/mco.2021.2250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976387PMC
May 2021

Soft implantable drug delivery device integrated wirelessly with wearable devices to treat fatal seizures.

Sci Adv 2021 Jan 1;7(1). Epub 2021 Jan 1.

Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea.

Personalized biomedical devices have enormous potential to solve clinical challenges in urgent medical situations. Despite this potential, a device for in situ treatment of fatal seizures using pharmaceutical methods has not been developed yet. Here, we present a novel treatment system for neurological medical emergencies, such as status epilepticus, a fatal epileptic condition that requires immediate treatment, using a soft implantable drug delivery device (SID). The SID is integrated wirelessly with wearable devices for monitoring electroencephalography signals and triggering subcutaneous drug release through wireless voltage induction. Because of the wireless integration, bulky rigid components such as sensors, batteries, and electronic circuits can be moved from the SID to wearables, and thus, the mechanical softness and miniaturization of the SID are achieved. The efficacy of the prompt treatment could be demonstrated with animal experiments in vivo, in which brain damages were reduced and survival rates were increased.
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http://dx.doi.org/10.1126/sciadv.abd4639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775752PMC
January 2021

Long-Term Outcomes and Sequelae Analysis of Intracranial Germinoma: Need to Reduce the Extended-Field Radiotherapy Volume and Dose to Minimize Late Sequelae.

Cancer Res Treat 2021 Jan 13. Epub 2021 Jan 13.

Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Purpose: We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities.

Materials And Methods: Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole-brain (WB), and whole-ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months.

Results: The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in ten patients (5.3 %) with a latency of 20 years (range, 4-26) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction.

Conclusion: Reduced dose and volume of extended-field rather than total dose or involved-field will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.
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http://dx.doi.org/10.4143/crt.2020.1052DOI Listing
January 2021

Absolute quantification of tumor-infiltrating immune cells in high-grade glioma identifies prognostic and radiomics values.

Cancer Immunol Immunother 2021 Jul 8;70(7):1995-2008. Epub 2021 Jan 8.

Department of Neurosurgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Purpose: To understand the tumor immune microenvironment precisely, it is important to secure the quantified data of tumor-infiltrating immune cells, since the immune cells are true working unit. We analyzed unit immune cell number per unit volume of core tumor tissue of high-grade gliomas (HGG) to correlate their immune microenvironment characteristics with clinical prognosis and radiomic signatures.

Methods: The number of tumor-infiltrating immune cells from 64 HGG core tissue were analyzed using flow cytometry and standardized. After sorting out patient groups according to diverse immune characteristics, the groups were tested if they have any clinical prognostic relevance and specific radiomic signature relationships. Sparse partial least square with discriminant analysis using multimodal magnetic resonance images was employed for all radiomic classifications.

Results: The median number of CD45 + cells per one gram of HGG core tissue counted 865,770 cells which was equivalent to 8.0% of total cells including tumor cells. There was heterogeneity in the distribution of immune cell subpopulations among patients. Overall survival was significantly better in T cell-deficient group than T cell-enriched group (p = 0.019), and T8 dominant group than T4 dominant group (p = 0.023). The number of tumor-associated macrophages (TAM) and M2-TAM was significantly decreased in isocitrate dehydrogenase mutated HGG. Radiomic signature classification showed good performance in predicting immune phenotypes especially with features extracted from apparent diffusion coefficient maps.

Conclusions: Absolute quantification of tumor-infiltrating immune cells confirmed the heterogeneity of immune microenvironment in HGG which harbors prognostic impact. This immune microenvironment could be predicted by radiomic signatures non-invasively.
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http://dx.doi.org/10.1007/s00262-020-02836-wDOI Listing
July 2021

Synthetic MRI: Technologies and Applications in Neuroradiology.

J Magn Reson Imaging 2020 Nov 13. Epub 2020 Nov 13.

Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.

Synthetic MRI is a technique that synthesizes contrast-weighted images from multicontrast MRI data. There have been advances in synthetic MRI since the technique was introduced. Although a number of synthetic MRI methods have been developed for quantifying one or more relaxometric parameters and for generating multiple contrast-weighted images, this review focuses on several methods that quantify all three relaxometric parameters (T , T , and proton density) and produce multiple contrast-weighted images. Acquisition, quantification, and image synthesis techniques are discussed for each method. We discuss the image quality and diagnostic accuracy of synthetic MRI methods and their clinical applications in neuroradiology. Based on this analysis, we highlight areas that need to be addressed for synthetic MRI to be widely implemented in the clinic. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 1.
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http://dx.doi.org/10.1002/jmri.27440DOI Listing
November 2020

Clinical and Genomic Characteristics of Adult Diffuse Midline Glioma.

Cancer Res Treat 2021 Apr 9;53(2):389-398. Epub 2020 Nov 9.

Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.

Purpose: The treatment outcomes and genomic profiles of diffuse midline glioma (DMG) in adult patients are rarely characterized. We performed a retrospective study to evaluate the clinicogenomic profiles of adult patients with brain DMG.

Materials And Methods: Patients aged ≥ 18 years diagnosed with brain DMG at Seoul National University Hospital were included. The clinicopathological parameters, treatment outcomes, survival, and genomic profiles using 82-gene targeted next-generation sequencing (NGS) were analyzed. The 6-month progression-free survival (PFS6) after radiotherapy and overall survival (OS) were evaluated.

Results: Thirty-three patients with H3-mutant brain DMG were identified. The median OS from diagnosis was 21.8 months (95% confidence interval [CI], 13.2 to not available [NA]) and involvement of the ponto-medullary area tended to have poor OS (median OS, 20.4 months [95% CI, 9.3 to NA] vs. 43.6 months [95% CI, 18.2 to NA]; p=0.07). Twenty-four patients (72.7%) received radiotherapy with or without temozolomide. The PFS6 rate was 83.3% (n=20). Patients without progression at 6 months showed significantly prolonged OS compared with those with progression at 6 months (median OS, 24.9 months [95% CI, 20.4 to NA] vs. 10.8 months [95% CI, 4.0 to NA]; p=0.02, respectively). Targeted NGS was performed in 13 patients with DMG, among whom nine (69.2%) harbored concurrent TP53 mutation. Two patients (DMG14 and DMG23) with PIK3CAR38S+E545K and KRASG12A mutations received matched therapies. Patient DMG14 received sirolimus with a PFS of 8.4 months.

Conclusion: PFS6 after radiotherapy was associated with prolonged survival in adult patients with DMG. Genome-based matched therapy may be an encouraging approach for progressive adult patients with DMG.
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http://dx.doi.org/10.4143/crt.2020.694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053865PMC
April 2021

Radiological assessment schedule for high-grade glioma patients during the surveillance period using parametric modeling.

Neuro Oncol 2021 05;23(5):837-847

Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine.

Background: An optimal radiological surveillance plan is crucial for high-grade glioma (HGG) patients, which is determined arbitrarily in daily clinical practice. We propose the radiological assessment schedule using a parametric model of standardized progression-free survival (PFS) curves.

Methods: A total of 277 HGG patients (178 glioblastoma [GBM] and 99 anaplastic astrocytoma [AA]) from a single institute who completed the standard treatment protocol were enrolled in this cohort study and retrospectively analyzed. The patients were stratified into each layered risk group by genetic signatures and residual mass or through recursive partitioning analysis. PFS curves were estimated using the piecewise exponential survival model. The criterion of a 10% progression rate among the remaining patients at each observation period was used to determine the optimal radiological assessment time point.

Results: The optimal follow-up intervals for MRI evaluations of isocitrate dehydrogenase (IDH) wild-type GBM was every 7.4 weeks until 120 weeks after the end of standard treatment, followed by a 22-week inflection period and every 27.6 weeks thereafter. For the IDH mutated GBM, scans every 13.2 weeks until 151 weeks are recommended. The optimal follow-up intervals were every 22.8 weeks for IDH wild-type AA, and 41.2 weeks for IDH mutated AA until 241 weeks. Tailored radiological assessment schedules were suggested for each layered risk group of the GBM and the AA patients.

Conclusions: The optimal schedule of radiological assessments for each layered risk group of patients with HGG could be determined from the parametric model of PFS.
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http://dx.doi.org/10.1093/neuonc/noaa250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099465PMC
May 2021

Diffusion and perfusion MRI radiomics obtained from deep learning segmentation provides reproducible and comparable diagnostic model to human in post-treatment glioblastoma.

Eur Radiol 2021 May 31;31(5):3127-3137. Epub 2020 Oct 31.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 43 Olympic-ro 88, Songpa-Gu, Seoul, 05505, South Korea.

Objectives: Deep learning-based automatic segmentation (DLAS) helps the reproducibility of radiomics features, but its effect on radiomics modeling is unknown. We therefore evaluated whether DLAS can robustly extract anatomical and physiological MRI features, thereby assisting in the accurate assessment of treatment response in glioblastoma patients.

Methods: A DLAS model was trained on 238 glioblastomas and validated on an independent set of 98 pre- and 86 post-treatment glioblastomas from two tertiary hospitals. A total of 1618 radiomics features from contrast-enhanced T1-weighted images (CE-T1w) and histogram features from apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) mapping were extracted. The diagnostic performance of radiomics features and ADC and CBV parameters for identifying treatment response was tested using area under the curve (AUC) from receiver operating characteristics analysis. Feature reproducibility was tested using a 0.80 cutoff for concordance correlation coefficients.

Results: Reproducibility was excellent for ADC and CBV features (ICC, 0.82-0.99) and first-order features (pre- and post-treatment, 100% and 94.1% remained), but lower for texture (79.0% and 69.1% remained) and wavelet-transformed (81.8% and 74.9% remained) features of CE-T1w. DLAS-based radiomics showed similar performance to human-performed segmentations in internal validation (AUC, 0.81 [95% CI, 0.64-0.99] vs. AUC, 0.81 [0.60-1.00], p = 0.80), but slightly lower performance in external validation (AUC, 0.78 [0.61-0.95] vs. AUC, 0.65 [0.46-0.84], p = 0.23).

Conclusion: DLAS-based feature extraction showed high reproducibility for first-order features from anatomical and physiological MRI, and comparable diagnostic performance to human manual segmentations in the identification of pseudoprogression, supporting the utility of DLAS in quantitative MRI analysis.

Key Points: • Deep learning-based automatic segmentation (DLAS) enables fast and robust feature extraction from diffusion- and perfusion-weighted MRI. • DLAS showed high reproducibility in first-order feature extraction from anatomical, diffusion, and perfusion MRI across two centers. • DLAS-based radiomics features showed comparable diagnostic accuracy to manual segmentations in post-treatment glioblastoma.
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http://dx.doi.org/10.1007/s00330-020-07414-3DOI Listing
May 2021

H3 G34-mutant high-grade glioma.

Brain Tumor Pathol 2021 Jan 29;38(1):4-13. Epub 2020 Sep 29.

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

H3F3A G34 (H3.3 G34)-mutant high-grade gliomas (HGG) are rare, and newly recognized infiltrating gliomas of the cerebral hemisphere. Here, we report the clinicopathological and molecular characteristics of four H3.3 G34-mutant gliomas in terms of its biological behavior compared to those of glioblastomas (GBMs) and H3 K27M-mutant diffuse midline gliomas (DMGs) of our hospital. The median age of the four patients with H3.3 G34 HGG was 44.5 years (14-66 years). Three patients had tumors in the cerebral hemisphere, whereas one patient had synchronous double tumors in the cerebral hemisphere and posterior fossa. All these tumors were high-grade glioma, but neither microvascular proliferation nor necrosis. They displayed uniform genetic and epigenetic signatures; ATRX-mutant, MGMT promoter-methylated, Olig2-negative, but IDH- and TERT promoter-wildtype. The median survival rate of H3.3 G34-mutant HGGs, IDH-was 23.5 months. In conclusion, H3.3 G34-mutant gliomas were unique HGGs with uniform genetic and epigenetic abnormalities, which suggested a single phylogenic origin. The median survival of H3.3 G34-mutant HGGs was better than those of IDH-wildtype GBMs and H3 K27M-mutant DMGs, but worse than that of IDH-mutant GBM. The tumor-infiltrating area and resectability may be the crucial parameters for the prognosis of the patients.
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http://dx.doi.org/10.1007/s10014-020-00378-8DOI Listing
January 2021

Machine Learning Model to Predict Pseudoprogression Versus Progression in Glioblastoma Using MRI: A Multi-Institutional Study (KROG 18-07).

Cancers (Basel) 2020 Sep 21;12(9). Epub 2020 Sep 21.

Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam 13620, Korea.

Some patients with glioblastoma show a worsening presentation in imaging after concurrent chemoradiation, even when they receive gross total resection. Previously, we showed the feasibility of a machine learning model to predict pseudoprogression (PsPD) versus progressive disease (PD) in glioblastoma patients. The previous model was based on the dataset from two institutions (termed as the Seoul National University Hospital (SNUH) dataset, = 78). To test this model in a larger dataset, we collected cases from multiple institutions that raised the problem of PsPD vs. PD diagnosis in clinics (Korean Radiation Oncology Group (KROG) dataset, = 104). The dataset was composed of brain MR images and clinical information. We tested the previous model in the KROG dataset; however, that model showed limited performance. After hyperparameter optimization, we developed a deep learning model based on the whole dataset ( = 182). The 10-fold cross validation revealed that the micro-average area under the precision-recall curve (AUPRC) was 0.86. The calibration model was constructed to estimate the interpretable probability directly from the model output. After calibration, the final model offers clinical probability in a web-user interface.
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http://dx.doi.org/10.3390/cancers12092706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564954PMC
September 2020

Revascularization Evaluation in Adult-Onset Moyamoya Disease after Bypass Surgery: Superselective Arterial Spin Labeling Perfusion MRI Compared with Digital Subtraction Angiography.

Radiology 2020 12 22;297(3):630-637. Epub 2020 Sep 22.

From the Departments of Radiology (I.H., R.E.Y., K.M.K., D.H.Y., T.J.Y., S.H.C., J..K., C.H.S.) and Neurosurgery (W.S.C., J.E.K.), Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea; and Department of Radiology, Seoul National University College of Medicine, Seoul, Korea (S.H.C., J..K., C.H.S.).

Background A superselective (SS) arterial spin labeling (ASL) MRI technique can be used to monitor the revascularization area as a supplementary or alternative modality to digital subtraction angiography (DSA), with the advantage of being noninvasive. Purpose To evaluate whether SS-ASL perfusion MRI could be used to visualize the revascularization area after combined direct and indirect bypass surgery in adults with moyamoya disease compared with DSA. Materials and Methods Patients diagnosed with moyamoya disease who underwent DSA and SS-ASL 6 months after surgery between June 2017 and November 2019 in a single institution were retrospectively evaluated. Subjective grading of the revascularization area and collateral grading in 10 Alberta Stroke Program Early CT Score (ASPECTS) locations were performed. The change in perfusion status in a subgroup that underwent both preoperative and postoperative SS-ASL studies was evaluated. Intermodality agreement was analyzed by using weighted κ statistics. Results Thirty-seven hemispheres from 33 patients (mean age, 39 years ± 12 [standard deviation]; 20 women) were evaluated. The intermodality agreement of the revascularization area grading was substantial (weighted κ = 0.70; 95% confidence interval [CI]: 0.37, 1.00). The overall intermodality agreement of the postoperative collateral grading in the 10 ASPECTS locations for all vessels was substantial (weighted κ = 0.77; 95% CI: 0.74, 0.80). For the presence of postoperative collateral supplied by the ipsilateral external carotid artery in 10 ASPECTS locations (a total of 370 locations) using DSA as a reference test, the SS-ASL showed a sensitivity of 92% (183 of 199 locations; 95% CI: 87%, 95%) and a specificity of 83% (142 of 171 locations; 95% CI: 77%, 88%). The overall intermodality agreement of the changes in perfusion status was moderate (weighted κ = 0.59; 95% CI: 0.54, 0.65). Conclusion Superselective arterial spin labeling imaging precisely depicted the revascularization territory in patients with moyamoya disease who underwent bypass surgery, and it showed the changes in the vascular supplying territories before and after bypass surgery. © RSNA, 2020 See also the editorial by Hendrikse in this issue.
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http://dx.doi.org/10.1148/radiol.2020201448DOI Listing
December 2020

Comparison of Genetic Profiles and Prognosis of High-Grade Gliomas Using Quantitative and Qualitative MRI Features: A Focus on G3 Gliomas.

Korean J Radiol 2021 02 10;22(2):233-242. Epub 2020 Sep 10.

Department of Neurology, Seoul National University College of Medicine, Seoul, Korea.

Objective: To evaluate the association of MRI features with the major genomic profiles and prognosis of World Health Organization grade III (G3) gliomas compared with those of glioblastomas (GBMs).

Materials And Methods: We enrolled 76 G3 glioma and 155 GBM patients with pathologically confirmed disease who had pretreatment brain MRI and major genetic information of tumors. Qualitative and quantitative imaging features, including volumetrics and histogram parameters, such as normalized cerebral blood volume (nCBV), cerebral blood flow (nCBF), and apparent diffusion coefficient (nADC) were evaluated. The G3 gliomas were divided into three groups for the analysis: with this isocitrate dehydrogenase ()-mutation, mutation and a -codeleted (IDHmut1p/19qdel), mutation, -nondeleted (IDHmut1p/19qnondel), and wildtype (IDHwt). A prediction model for the genetic profiles of G3 gliomas was developed and validated on a separate cohort. Both the quantitative and qualitative imaging parameters and progression-free survival (PFS) of G3 gliomas were compared and survival analysis was performed. Moreover, the imaging parameters and PFS between IDHwt G3 gliomas and GBMs were compared.

Results: IDHmut G3 gliomas showed a larger volume ( = 0.017), lower nCBF ( = 0.048), and higher nADC ( = 0.007) than IDHwt. Between the IDHmut tumors, IDHmut1p/19qdel G3 gliomas had higher nCBV ( = 0.024) and lower nADC ( = 0.002) than IDHmut1p/19qnondel G3 gliomas. Moreover, IDHmut1p/19qdel tumors had the best prognosis and IDHwt tumors had the worst prognosis among G3 gliomas ( < 0.001). PFS was significantly associated with the 95th percentile values of nCBV and nCBF in G3 gliomas. There was no significant difference in neither PFS nor imaging features between IDHwt G3 gliomas and IDHwt GBMs.

Conclusion: We found significant differences in MRI features, including volumetrics, CBV, and ADC, in G3 gliomas, according to mutation and codeletion status, which can be utilized for the prediction of genomic profiles and the prognosis of G3 glioma patients. The MRI signatures and prognosis of IDHwt G3 gliomas tend to follow those of IDHwt GBMs.
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http://dx.doi.org/10.3348/kjr.2020.0011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817637PMC
February 2021

Advances in drug delivery technology for the treatment of glioblastoma multiforme.

J Control Release 2020 12 4;328:350-367. Epub 2020 Sep 4.

Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea; School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:

Glioblastoma multiforme (GBM) is a particularly aggressive and malignant type of brain tumor, notorious for its high recurrence rate and low survival rate. The treatment of GBM is challenging mainly because several issues associated with the GBM microenvironment have not yet been resolved. These obstacles originate from a variety of factors such as genetics, anatomy, and cytology, all of which collectively hinder the treatment of GBM. Recent advances in materials and device engineering have presented new perspectives with regard to unconventional drug administration methods for GBM treatment. Such novel drug delivery approaches, based on the clear understanding of the intrinsic properties of GBM, have shown promise in overcoming some of the obstacles. In this review, we first recapitulate the first-line therapy and clinical challenges in the current treatment of GBM. Afterwards, we introduce the latest technological advances in drug delivery strategies to improve the efficiency for GBM treatment, mainly focusing on materials and devices. We describe such efforts by classifying them into two categories, systemic and local drug delivery. Finally, we discuss unmet challenges and prospects for the clinical translation of these drug delivery technologies.
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http://dx.doi.org/10.1016/j.jconrel.2020.09.002DOI Listing
December 2020

Reduced Brainstem Volume After Mild Traumatic Brain Injury.

Am J Phys Med Rehabil 2021 05;100(5):473-482

From the Department of Rehabilitation Medicine (EK, HGS, HHL, SHL, SJY, M-GK, B-MO), Biomedical Research Institute (EK), Department of Radiology (SHC, R-EY), and Department of Neurosurgery (W-SC), Seoul National University Hospital, Seoul, Korea; Department of Rehabilitation Medicine, Konkuk University School of Medicine and Konkuk University Medical Center, Seoul, Korea (HHL); Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (SHL); Department of Radiology (SHC, R-EY), Department of Rehabilitation Medicine (B-MO), and Neuroscience Research Institute (B-MO), Seoul National University College of Medicine, Seoul, Korea; Institute on Aging, Seoul National University, Seoul, Korea (B-MO); and National Traffic Injury Rehabilitation Hospital, Yangpyeong, Korea (B-MO).

Objective: The aims of this study were to investigate changes in regional brain volume after concussion (mild traumatic brain injury) and to examine the relationship between change in brain volume and cognitive deficits.

Design: Twenty-eight patients with mild traumatic brain injury and 27 age-matched controls were included in this study. Magnetic resonance imaging (3 T) data were obtained from the participants. Structural brain volume changes were examined using tensor-based morphometry, which identifies regional structural differences in the whole brain, including cerebrospinal fluid, gray matter, and white matter. Volume contraction and expansion were compared between groups using a two-sample t test. The association between time post-injury or neurocognitive function and volumetric changes was examined using regression analysis.

Results: Individuals with mild traumatic brain injury exhibited volume reduction in the brainstem, including the pontine reticular formation. Regional cerebral volume changes were not associated with time post-injury but were significantly associated with neurocognitive function, especially with executive card sorting test, forward digit span test, and performance on verbal learning test. The greater regional cerebral volume was associated with better cognitive performance after mild traumatic brain injury.

Conclusion: Decreased brainstem volume may indicate its vulnerability to traumatic injury, and cerebral volume in specific regions was positively associated with patients' cognitive function after injury.
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http://dx.doi.org/10.1097/PHM.0000000000001580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032213PMC
May 2021

Intracranial Metaplastic Meningioma : Clinical and Radiological Characteristics of 11 Cases.

J Korean Neurosurg Soc 2020 Sep 1;63(5):657-663. Epub 2020 Sep 1.

Department of Pathology, Seoul National University Hospital, Seoul, Korea.

Objective: Metaplastic meningioma is an extremely rare subtype of World Health Organization (WHO) grade I meningioma. It has distinctive histological subtypes according to its own mesenchymal components. Owing to its scarcity, clinical or radiological features of a metaplastic meningioma are poorly described.

Methods: Between 2004 and 2018, we analyzed total 1814 cases surgically proven meningioma for 15 years. Among them, metaplastic meningioma was diagnosed in 11 cases. Magnetic resonance images were taken for all patients, and computed tomography scan was taken for 10 patients.

Results: WHO grade I meningiomas were 1376 cases (75.9%), 354 cases (19.5%) in WHO grade II, and 84 cases (4.6%) in WHO grade III meningiomas. Metaplastic meningioma was 11 cases as 0.8% of WHO grade I meningioma and 0.6% of entire meningiomas for 15 years. Among the entire 11 metaplastic meningiomas, five tumors (45%) were diagnosed as a lipomatous subtype with rich fat components, four (36%) as an osseous subtype with extensive bone formation and two (18%) as a xanthomatous subtype. There was no cartilaginous subtype metaplastic meningioma in our study. Lipomatous and osseous metaplastic meningioma have peculiar radiological characteristics according to mesenchymal components.

Conclusion: We investigated a rare metaplastic meningioma subtype based on our 15-year surgical experience with meningiomas. Further investigation will be necessary for the clear clarification of tumor nature of this rare tumor.
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http://dx.doi.org/10.3340/jkns.2020.0151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477148PMC
September 2020
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