Assessment of Esophageal Reconstruction via Bioreactor Cultivation of a Synthetic Scaffold in a Canine Model

Objectives@#. Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model. @*Methods@#. We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning technique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold, and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreactor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long resection) in a canine model. @*Results@#. Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly and circumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was confirmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed that there were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Significant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin immunostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months. @*Conclusion@#. Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach for esophageal tissue engineering.

Myelin Content in Mild Traumatic Brain Injury Patients with Post-Concussion Syndrome: Quantitative Assessment with a Multidynamic Multiecho Sequence

Objective@#This study aimed to explore the myelin volume change in patients with mild traumatic brain injury (mTBI) with post-concussion syndrome (PCS) using a multidynamic multiecho (MDME) sequence and automatic whole-brain segmentation. @*Materials and Methods@#Forty-one consecutive mTBI patients with PCS and 29 controls, who had undergone MRI including the MDME sequence between October 2016 and April 2018, were included. Myelin volume fraction (MVF) maps were derived from the MDME sequence. After three dimensional T1-based brain segmentation, the average MVF was analyzed at the bilateral cerebral white matter (WM), bilateral cerebral gray matter (GM), corpus callosum, and brainstem. The Mann–Whitney U-test was performed to compare MVF and myelin volume between patients with mTBI and controls. Myelin volume was correlated with neuropsychological test scores using the Spearman rank correlation test. @*Results@#The average MVF at the bilateral cerebral WM was lower in mTBI patients with PCS (median [interquartile range], 25.2% [22.6%–26.4%]) than that in controls (26.8% [25.6%–27.8%]) (p = 0.004). The region-of-interest myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (1.87 cm3 [1.70–2.05 cm3 ] vs. 2.21 cm3 [1.86– 3.46 cm3 ]; p = 0.003) and brainstem (9.98 cm3 [9.45–11.00 cm3 ] vs. 11.05 cm3 [10.10–11.53 cm3 ]; p = 0.015). The total myelin volume was lower in mTBI patients with PCS than that in controls at the corpus callosum (0.45 cm3 [0.39–0.48 cm3 ] vs. 0.48 cm3 [0.45–0.54 cm3 ]; p = 0.004) and brainstem (1.45 cm3 [1.28–1.59 cm3 ] vs. 1.54 cm3 [1.42–1.67 cm3 ]; p = 0.042). No significant correlation was observed between myelin volume parameters and neuropsychological test scores, except for the total myelin volume at the bilateral cerebral WM and verbal learning test (delayed recall) (r = 0.425; p = 0.048). @*Conclusion@#MVF quantified from the MDME sequence was decreased at the bilateral cerebral WM in mTBI patients with PCS. The total myelin volumes at the corpus callosum and brainstem were decreased in mTBI patients with PCS due to atrophic changes.

Local Drug Delivery Strategies for Glioblastoma Treatment

Glioblastoma multiforme (GBM) is a brain tumor notorious for its malignancy. The key reason for the limited efficacy of standard treatment is the high recurrence rate of GBM, even after surgical resection. Hence, intensive postsurgical chemical therapies, such as the systemic delivery of various drugs and/ or drug combinations, are typically followed after surgery. However, overcoming the blood-brain barrier by systemic administration to efficiently deliver drugs to the brain tumor remains a daunting goal. Therefore, various local drug delivery methods showing potential for improved therapeutic efficacy have been proposed. In particular, the recent application of electronic devices for the controlled delivery of chemotherapy drugs to GBM tissue has attracted attention. We herein review the recent progress of local drug delivery strategies, including electronics-assisted strategies, at the research and commercial level. We also present a brief discussion of the unsolved challenges and future research direction of localized chemotherapy methods for GBM.

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

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 (Ktrans), fractional volume of vascular plasma space (Vp), and fractional volume of extravascular extracellular space (Ve) 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 p < 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; p = 0.004 and hazard ratio, 0.34; p = 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.

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

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 (Ktrans ), volume of the vascular plasma space (vp), and the volume of the extravascular extracellular space (ve) 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 Ktrans , ve, and vp were significantly higher in the fixed value method than in the T1 map method. In the normal-appearing occipital WM, the mean values of ve and vp were significantly higher in the fixed value method. In the putamen and head of the caudate nucleus, the mean values of Ktrans , ve, and vp 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.

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

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 Ktrans, mean Ktrans, and median Ve were significant predictors of early progression as identified by the ROC curve analysis (area under the ROC curve [AUC] = 0.704, p = 0.005; AUC = 0.684, p = 0.021; and AUC = 0.670, p = 0.0325, respectively). Univariable Cox regression analysis of the above three parametric values showed that the 95th PV of Ktrans and the mean Ktrans were significant predictors of early progression (hazard ratio [HR] = 1.06, p = 0.009; HR = 1.25, p = 0.017, respectively). Multivariable Cox regression analysis, which also incorporated clinical parameters, revealed that the 95th PV of Ktrans was the sole significant independent predictor of early progression (HR = 1.062, p < 0.009). @*Conclusion@#The 95th PV of Ktrans from the non-enhancing, T2-HSI lesions of GBM is a potential prognostic marker for disease progression.

Cerebrovascular Reservoir and Arterial Transit Time Changes Assessed by Acetazolamide-Challenged Multi-Phase Arterial Spin Labeling Perfusion MRI in Chronic Cerebrovascular Steno-Occlusive Disease

Purpose@#To explore cerebrovascular reservoir (CVR) and arterial transit time (ATT) changes using acetazolamide-challenged multi-phase arterial spin labeling (MP-ASL) perfusion-weighted MRI in chronic cerebrovascular steno-occlusive disease. @*Materials and Methods@#This retrospective study enrolled patients with chronic steno-occlusion who underwent acetazolamide-challenged MP-ASL between June 2019 and October 2020.Cerebral blood flow, CVR, basal ATT, and ATT changes associated with severe stenosis, total occlusion, and chronic infarction lesions were compared. @*Results@#There were 32 patients (5 with bilateral steno-occlusion) in our study sample. The CVR was significantly reduced during total occlusion compared with severe stenosis (26.2% ± 28.8% vs. 41.4% ± 34.1%, respectively, p = 0.004). The ATT changes were not significantly different (p = 0.717). The CVR was marginally lower in patients with chronic infarction (29.6% ± 39.1% vs. 38.9% ± 28.7%, respectively, p = 0.076). However, the ATT was less shortened in pa-tients with chronic infarction (-54 ± 135 vs. -117 ± 128 ms, respectively, p = 0.013). @*Conclusion@#Acetazolamide-challenged MP-ASL provides an MRI-based CVR evaluation tool for chronic steno-occlusive disease.

Assessment of Mild Cognitive Impairment in Elderly Subjects Using a Fully Automated Brain Segmentation Software

Purpose@#Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD). Brain atrophy in this disease spectrum begins in the medial temporal lobe structure, which can be recognized by magnetic resonance imaging. To overcome the unsatisfactory inter-observer reliability of visual evaluation, quantitative brain volumetry has been developed and widely investigated for the diagnosis of MCI and AD. The aim of this study was to assess the prediction accuracy of quantitative brain volumetry using a fully automated segmentation software package, NeuroQuant®, for the diagnosis of MCI. @*Materials and Methods@#A total of 418 subjects from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease cohort were included in our study. Each participant was allocated to either a cognitively normal old group (n = 285) or an MCI group (n = 133). Brain volumetric data were obtained from T1-weighted images using the NeuroQuant software package. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to investigate relevant brain regions and their prediction accuracies. @*Results@#Multivariate logistic regression analysis revealed that normative percentiles of the hippocampus (P < 0.001), amygdala (P = 0.003), frontal lobe (P = 0.049), medial parietal lobe (P = 0.023), and third ventricle (P = 0.012) were independent predictive factors for MCI. In ROC analysis, normative percentiles of the hippocampus and amygdala showed fair accuracies in the diagnosis of MCI (area under the curve: 0.739 and 0.727, respectively). @*Conclusion@#Normative percentiles of the hippocampus and amygdala provided by the fully automated segmentation software could be used for screening MCI with a reasonable post-processing time. This information might help us interpret structural MRI in patients with cognitive impairment.

The Emerging Role of Fast MR Techniques in Traumatic Brain Injury

Post-concussion syndrome (PCS) following mild traumatic brain injury (mTBI) is a major factor that contributes to the increased socioeconomic burden caused by TBI.Myelin loss has been implicated in the development of PCS following mTBI. Diffusion tensor imaging (DTI), a traditional imaging modality for the evaluation of axonal and myelin integrity in mTBI, has intrinsic limitations, including its lack of specificity and its time-consuming and labor-intensive post-processing analysis. More recently, various fast MR techniques based on multicomponent relaxometry (MCR), including QRAPMASTER, mcDESPOT, and MDME sequences, have been developed. These MCRbased sequences can provide myelin water fraction/myelin volume fraction, a quantitative parameter more specific to myelin, which might serve as a surrogate marker of myelin volume, in a clinically feasible time. In this review, we summarize the clinical application of the MCR-based fast MR techniques in mTBI patients.

Clinical and Genomic Characteristics of Adult Diffuse Midline Glioma / Journal of the Korean Cancer Association, 대한암학회지

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.

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

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 (Ktrans), fractional volume of vascular plasma space (Vp), and fractional volume of extravascular extracellular space (Ve) 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 p < 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; p = 0.004 and hazard ratio, 0.34; p = 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.

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

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 (Ktrans ), volume of the vascular plasma space (vp), and the volume of the extravascular extracellular space (ve) 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 Ktrans , ve, and vp were significantly higher in the fixed value method than in the T1 map method. In the normal-appearing occipital WM, the mean values of ve and vp were significantly higher in the fixed value method. In the putamen and head of the caudate nucleus, the mean values of Ktrans , ve, and vp 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.

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

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 Ktrans, mean Ktrans, and median Ve were significant predictors of early progression as identified by the ROC curve analysis (area under the ROC curve [AUC] = 0.704, p = 0.005; AUC = 0.684, p = 0.021; and AUC = 0.670, p = 0.0325, respectively). Univariable Cox regression analysis of the above three parametric values showed that the 95th PV of Ktrans and the mean Ktrans were significant predictors of early progression (hazard ratio [HR] = 1.06, p = 0.009; HR = 1.25, p = 0.017, respectively). Multivariable Cox regression analysis, which also incorporated clinical parameters, revealed that the 95th PV of Ktrans was the sole significant independent predictor of early progression (HR = 1.062, p < 0.009). @*Conclusion@#The 95th PV of Ktrans from the non-enhancing, T2-HSI lesions of GBM is a potential prognostic marker for disease progression.

Cerebrovascular Reservoir and Arterial Transit Time Changes Assessed by Acetazolamide-Challenged Multi-Phase Arterial Spin Labeling Perfusion MRI in Chronic Cerebrovascular Steno-Occlusive Disease

Purpose@#To explore cerebrovascular reservoir (CVR) and arterial transit time (ATT) changes using acetazolamide-challenged multi-phase arterial spin labeling (MP-ASL) perfusion-weighted MRI in chronic cerebrovascular steno-occlusive disease. @*Materials and Methods@#This retrospective study enrolled patients with chronic steno-occlusion who underwent acetazolamide-challenged MP-ASL between June 2019 and October 2020.Cerebral blood flow, CVR, basal ATT, and ATT changes associated with severe stenosis, total occlusion, and chronic infarction lesions were compared. @*Results@#There were 32 patients (5 with bilateral steno-occlusion) in our study sample. The CVR was significantly reduced during total occlusion compared with severe stenosis (26.2% ± 28.8% vs. 41.4% ± 34.1%, respectively, p = 0.004). The ATT changes were not significantly different (p = 0.717). The CVR was marginally lower in patients with chronic infarction (29.6% ± 39.1% vs. 38.9% ± 28.7%, respectively, p = 0.076). However, the ATT was less shortened in pa-tients with chronic infarction (-54 ± 135 vs. -117 ± 128 ms, respectively, p = 0.013). @*Conclusion@#Acetazolamide-challenged MP-ASL provides an MRI-based CVR evaluation tool for chronic steno-occlusive disease.

Assessment of Mild Cognitive Impairment in Elderly Subjects Using a Fully Automated Brain Segmentation Software

Purpose@#Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD). Brain atrophy in this disease spectrum begins in the medial temporal lobe structure, which can be recognized by magnetic resonance imaging. To overcome the unsatisfactory inter-observer reliability of visual evaluation, quantitative brain volumetry has been developed and widely investigated for the diagnosis of MCI and AD. The aim of this study was to assess the prediction accuracy of quantitative brain volumetry using a fully automated segmentation software package, NeuroQuant®, for the diagnosis of MCI. @*Materials and Methods@#A total of 418 subjects from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease cohort were included in our study. Each participant was allocated to either a cognitively normal old group (n = 285) or an MCI group (n = 133). Brain volumetric data were obtained from T1-weighted images using the NeuroQuant software package. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to investigate relevant brain regions and their prediction accuracies. @*Results@#Multivariate logistic regression analysis revealed that normative percentiles of the hippocampus (P < 0.001), amygdala (P = 0.003), frontal lobe (P = 0.049), medial parietal lobe (P = 0.023), and third ventricle (P = 0.012) were independent predictive factors for MCI. In ROC analysis, normative percentiles of the hippocampus and amygdala showed fair accuracies in the diagnosis of MCI (area under the curve: 0.739 and 0.727, respectively). @*Conclusion@#Normative percentiles of the hippocampus and amygdala provided by the fully automated segmentation software could be used for screening MCI with a reasonable post-processing time. This information might help us interpret structural MRI in patients with cognitive impairment.

The Emerging Role of Fast MR Techniques in Traumatic Brain Injury

Post-concussion syndrome (PCS) following mild traumatic brain injury (mTBI) is a major factor that contributes to the increased socioeconomic burden caused by TBI.Myelin loss has been implicated in the development of PCS following mTBI. Diffusion tensor imaging (DTI), a traditional imaging modality for the evaluation of axonal and myelin integrity in mTBI, has intrinsic limitations, including its lack of specificity and its time-consuming and labor-intensive post-processing analysis. More recently, various fast MR techniques based on multicomponent relaxometry (MCR), including QRAPMASTER, mcDESPOT, and MDME sequences, have been developed. These MCRbased sequences can provide myelin water fraction/myelin volume fraction, a quantitative parameter more specific to myelin, which might serve as a surrogate marker of myelin volume, in a clinically feasible time. In this review, we summarize the clinical application of the MCR-based fast MR techniques in mTBI patients.

Clinical and Genomic Characteristics of Adult Diffuse Midline Glioma / Journal of the Korean Cancer Association, 대한암학회지

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.

Blood-Brain Barrier Disruption in Mild Traumatic Brain Injury Patients with Post-Concussion Syndrome: Evaluation with Region-Based Quantification of Dynamic Contrast-Enhanced MR Imaging Parameters Using Automatic Whole-Brain Segmentation

Objective@#This study aimed to investigate the blood-brain barrier (BBB) disruption in mild traumatic brain injury (mTBI) patients with post-concussion syndrome (PCS) using dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging and automatic whole brain segmentation. @*Materials and Methods@#Forty-two consecutive mTBI patients with PCS who had undergone post-traumatic MR imaging, including DCE MR imaging, between October 2016 and April 2018, and 29 controls with DCE MR imaging were included in this retrospective study. After performing three-dimensional T1-based brain segmentation with FreeSurfer software (Laboratory for Computational Neuroimaging), the mean Ktrans and vp from DCE MR imaging (derived using the Patlak model and extended Tofts and Kermode model) were analyzed in the bilateral cerebral/cerebellar cortex, bilateral cerebral/cerebellar white matter (WM), and brainstem. Ktrans values of the mTBI patients and controls were calculated using both models to identify the model that better reflected the increased permeability owing to mTBI (tendency toward higher Ktrans values in mTBI patients than in controls). The Mann-Whitney U test and Spearman rank correlation test were performed to compare the mean Ktrans and vp between the two groups and correlate Ktrans and vp with neuropsychological tests for mTBI patients. @*Results@#Increased permeability owing to mTBI was observed in the Patlak model but not in the extended Tofts and Kermode model. In the Patlak model, the mean Ktrans in the bilateral cerebral cortex was significantly higher in mTBI patients than in controls (p = 0.042). The mean vp values in the bilateral cerebellar WM and brainstem were significantly lower in mTBI patients than in controls (p = 0.009 and p = 0.011, respectively). The mean Ktrans of the bilateral cerebral cortex was significantly higher in patients with atypical performance in the auditory continuous performance test (commission errors) than in average or good performers (p = 0.041). @*Conclusion@#BBB disruption, as reflected by the increased Ktrans and decreased vp values from the Patlak model, was observed throughout the bilateral cerebral cortex, bilateral cerebellar WM, and brainstem in mTBI patients with PCS.

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

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 (IDH)-mutation, IDH mutation and a chromosome arm 1p/19q-codeleted (IDHmut1p/19qdel), IDH mutation, 1p/19q-nondeleted (IDHmut1p/19qnondel), and IDH 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 (p = 0.017), lower nCBF (p = 0.048), and higher nADC (p = 0.007) than IDHwt. Between the IDHmut tumors, IDHmut1p/19qdel G3 gliomas had higher nCBV (p = 0.024) and lower nADC (p = 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 (p < 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 IDH mutation and 1p/19q 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.

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

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 Ktrans and Vp 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 (Ktrans and Vp , both, p = 0.062), left thalamus and in left putamen (Ktrans , p = 0.062), and left insula and right amygdala (Vp , p = 0.062), but not in the control placebo group. The increment of the Ktrans value in the left thalamus from the baseline was highly correlated with the change of the ADAS scores (r = −0.900, p = 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.