Publications by authors named "Chul Ho Sohn"

182 Publications

Joint Reconstruction of Vascular Structure and Function Maps in Dynamic Contrast Enhanced MRI Using Vascular Heterogeneity Priors.

IEEE Trans Med Imaging 2021 Aug 11;PP. Epub 2021 Aug 11.

This work introduces a novel, joint reconstruction of vascular structure and microvascular function maps directly from highly undersampled data in k-t space using vascular heterogeneity priors for high-definition, dynamic contrast-enhanced (DCE) MRI. In DCE MRI, arteries and veins are characterized by rapid, high uptake and wash-out of contrast agents (CA). On the other hand, depending on CA uptake and wash-out signal patterns, capillary tissues can be categorized into highly perfused, moderately perfused, and necrotic regions. Given the above considerations, macrovascular maps are generated as a prior to differentiate penalties on arteries relative to capillary tissues during image reconstruction. Furthermore, as a microvascular prior, contrast dynamics in capillary regions are represented in a low dimensional space using a finite number of basic vectors that reflect actual tissue-specific signal patterns. Both vascular structure and microvascular function maps are jointly estimated by solving a constrained optimization problem in which the above vascular heterogeneity priors are represented by spatially weighted nonnegative matrix factorization. Retrospective and prospective experiments are performed to validate the effectiveness of the proposed method in generating well-defined vascular structure and microvascular function maps for patients with brain tumor at high reduction factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TMI.2021.3104016DOI Listing
August 2021

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

Korean J Radiol 2021 Sep 14;22(9):1514-1524. Epub 2021 Jul 14.

Department of Radiology, 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2020.1433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390822PMC
September 2021

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

Radiology 2021 Sep 22;300(3):661-668. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2021203784DOI Listing
September 2021

Renal Safety of Repeated Intravascular Administrations of Iodinated or Gadolinium-Based Contrast Media within a Short Interval.

Korean J Radiol 2021 Sep 1;22(9):1547-1554. Epub 2021 Jun 1.

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

Objective: We aimed to investigate whether repeated intravascular administration of iodinated contrast media (ICM) or gadolinium-based contrast agents (GBCAs) within a short interval was associated with an increased risk of post-contrast acute kidney injury (PC-AKI).

Materials And Methods: This retrospective study included 300 patients (mean age ± standard deviation, 68.5 ± 8.1 years; 131 male and 169 female) who had undergone at least one ICM-enhanced perfusion brain CT scan, had their baseline and follow-up serum creatinine levels available, and had not undergone additional contrast-enhanced examinations 72 hours before and after a time window of interest were included. The study population was divided into three groups: single-dose group and groups of patients who had received multiple contrast administrations in the time window of interest with the minimum contrast repeat interval either within 4 hours (0-4-hour group) or between 4 to 48 hours (4-48-hour group). Multivariable logistic regression analysis was conducted to evaluate the association between AKI and repeated ICM administrations. A similar supplementary analysis was performed including both ICM and GBCA.

Results: When ICM was only considered ignoring GBCA, among 300 patients, 207 patients received a single dose of ICM, 58 had repeated doses within 4 hours (0-4-hour group), and 35 patients had repeated doses between 4 to 48 hours (4-48-hour group). Most patients (> 95%) had a baseline estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m². AKI occurred in 7.2%, 13.8%, and 8.6% of patients in the single-dose, 0-4-hour, and 4-48-hour groups, respectively. In the 0-4-hour and 4-48-hour groups, additional exposure to ICM was not associated with AKI after adjusting for comorbidities and nephrotoxic drugs (all values > 0.05).

Conclusion: Repeated intravascular administrations of ICM within a short interval did not increase the risk of AKI in our study patients suspected of acute stroke with a baseline eGFR of ≥ 30 mL/min/1.73 m².
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2020.1153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390825PMC
September 2021

Imaging the Substantia Nigra in Parkinson Disease and Other Parkinsonian Syndromes.

Radiology 2021 Aug 8;300(2):260-278. Epub 2021 Jun 8.

From the Departments of Radiology (Y.J.B., B.S.C., S.J.C., J.H.K.), Neurology (J.M.K., J.H.C.), and Nuclear Medicine (Y.S.S.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea; Departments of Radiology (C.H.S.) and Neurology (B.J.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; and Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea (Y.N.).

Parkinson disease is characterized by dopaminergic cell loss in the substantia nigra of the midbrain. There are various imaging markers for Parkinson disease. Recent advances in MRI have enabled elucidation of the underlying pathophysiologic changes in the nigral structure. This has contributed to accurate and early diagnosis and has improved disease progression monitoring. This article aims to review recent developments in nigral imaging for Parkinson disease and other parkinsonian syndromes, including nigrosome imaging, neuromelanin imaging, quantitative iron mapping, and diffusion-tensor imaging. In particular, this article examines nigrosome imaging using 7-T MRI and 3-T susceptibility-weighted imaging. Finally, this article discusses volumetry and its clinical importance related to symptom manifestation. This review will improve understanding of recent advancements in nigral imaging of Parkinson disease. Published under a CC BY 4.0 license.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2021203341DOI Listing
August 2021

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

Neurobiol Aging 2021 09 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2021.04.015DOI Listing
September 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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 08 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 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, = 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 Ktrans and the mean Ktrans 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 Ktrans was the sole significant independent predictor of early progression (HR = 1.062, < 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2020.1272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316772PMC
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 08 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2020.1201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316777PMC
August 2021

Cerebrospinal fluid dynamics correlate with neurogenic claudication in lumbar spinal stenosis.

PLoS One 2021 12;16(5):e0250742. Epub 2021 May 12.

Department of Brain and Cognitive Engineering, Korea University, Seoul, South Korea.

Neurogenic claudication is a typical manifestation of lumbar spinal stenosis (LSS). However, its pathophysiology is still unclear. The severity of clinical symptoms has been shown not to correlate with the degree of structural stenosis. Altered cerebrospinal fluid (CSF) flow has been suggested as one of the causative factors of LSS. The objectives of this study were to compare CSF dynamics at the lumbosacral level between patients with LSS and healthy controls and to investigate whether CSF dynamics parameters explain symptom severity in LSS. Phase-contrast magnetic resonance imaging (PC-MRI) was conducted to measure CSF dynamics in 18 healthy controls and 9 patients with LSS. Cephalic peak, caudal peak, and peak-to-peak CSF velocities were evaluated at the lumbosacral level in the patients and controls. The power of CSF dynamics parameters to predict symptom severity was determined using a linear regression analysis adjusted for demographic and structural variables. Significantly attenuated CSF flow velocity was observed in the patients compared with the controls. The cephalic peak, caudal peak, and peak-to-peak velocities at the lumbar level were greater in the controls than in the patients (p<0.001). The predictive power increased most when the peak-to-peak velocity was added (adjusted R2 = 0.410) to the model with age, body mass index, and the minimum anterior-posterior diameter (adjusted R2 = 0.306), and the peak-to-peak velocity was the only statistically significant variable. CSF dynamics variables showed an association with the severity of LSS symptoms, independent of structural stenosis. PC-MRI can help to further our understanding of the pathophysiology of neurogenic claudication and support the diagnosis of LSS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250742PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115821PMC
May 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-89218-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113258PMC
May 2021

Synergistic Effect of Serum Homocysteine and Diabetes Mellitus on Brain Alterations.

J Alzheimers Dis 2021 ;81(1):287-295

Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea.

Background: Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM.

Objective: This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-β and tau deposition, and small vessel disease (SVD) related to cognitive impairments.

Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11C] Pittsburgh Compound B (PiB) PET, [18F] AV-1451 PET, and brain MRI.

Results: The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer's disease (AD) pathologies, including amyloid-β and tau deposition, nor white matter hyperintensity volume as a measure of SVD.

Conclusion: The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-210036DOI Listing
September 2021

Blood Hemoglobin, Alzheimer Pathologies, and Cognitive Impairment: A Cross-Sectional Study.

Front Aging Neurosci 2021 24;13:625511. Epub 2021 Feb 24.

Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.

Despite known associations between low blood hemoglobin level and Alzheimer's disease (AD) or cognitive impairment, the underlying neuropathological links are poorly understood. We aimed to examine the relationships of blood hemoglobin levels with AD pathologies (i.e., cerebral beta-amyloid [Aβ] deposition, tau deposition, and AD-signature degeneration) and white matter hyperintensities (WMHs), which are a measure of cerebrovascular injury. We also investigated the association between hemoglobin level and cognitive performance, and then assessed whether such an association is mediated by brain pathologies. A total of 428 non-demented older adults underwent comprehensive clinical assessments, hemoglobin level measurement, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Episodic memory score and global cognition scores were also measured. A lower hemoglobin level was significantly associated with reduced AD-signature cerebral glucose metabolism (AD-CM), but not Aβ deposition, tau deposition, or WMH volume. A lower hemoglobin level was also significantly associated with poorer episodic memory and global cognition scores, but such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a moderating effect. The present findings suggest that low blood hemoglobin in older adults is associated with cognitive decline via reduced brain metabolism, which seems to be independent of those aspects of AD-specific protein pathologies and cerebrovascular injury that are reflected in PET and MRI measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2021.625511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943867PMC
February 2021

Genetic associations of in vivo pathology influence Alzheimer's disease susceptibility.

Alzheimers Res Ther 2020 11 19;12(1):156. Epub 2020 Nov 19.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.

Introduction: Although the heritability of sporadic Alzheimer's disease (AD) is estimated to be 60-80%, addressing the genetic contribution to AD risk still remains elusive. More specifically, it remains unclear whether genetic variants are able to affect neurodegenerative brain features that can be addressed by in vivo imaging techniques.

Methods: Targeted sequencing analysis of the coding and UTR regions of 132 AD susceptibility genes was performed. Neuroimaging data using C-Pittsburgh Compound B positron emission tomography (PET), F-fluorodeoxyglucose PET, and MRI that are available from the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease) cohort were acquired. A total of 557 participants consisted of 336 cognitively normal (CN) adults, 137 mild cognitive impairment (MCI), and 84 AD dementia (ADD) groups.

Results: We called 5391 high-quality single nucleotide variants (SNVs) on AD susceptibility genes and selected significant associations between variants and five in vivo AD pathologies: (1) amyloid β (Aβ) deposition, (2) AD-signature region cerebral glucose metabolism (AD-Cm), (3) posterior cingulate cortex (PCC) cerebral glucose metabolism (PCC-Cm), (4) AD-signature region cortical thickness (AD-Ct), and (5) hippocampal volume (Hv). The association analysis for common variants (allele frequency (AF) > 0.05) yielded several novel loci associated with Aβ deposition (PIWIL1-rs10848087), AD-Cm (NME8-rs2722372 and PSEN2-rs75733498), AD-Ct (PSEN1-rs7523) and, Hv (CASS4-rs3746625). Meanwhile, in a gene-based analysis for rare variants (AF < 0.05), cases carrying rare variants in LPL, FERMT2, NFAT5, DSG2, and ITPR1 displayed associations with the neuroimaging features. Exploratory voxel-based brain morphometry between the variant carriers and non-carriers was performed subsequently. Finally, we document a strong association of previously reported APOE variants with the in vivo AD pathologies and demonstrate that the variants exert a causal effect on AD susceptibility via neuroimaging features.

Conclusions: This study provides novel associations of genetic factors to Aβ accumulation and AD-related neurodegeneration to influence AD susceptibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-020-00722-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678113PMC
November 2020

Superselective pseudocontinuous arterial spin labeling in patients with meningioma: utility in prediction of feeding arteries and preoperative embolization feasibility.

J Neurosurg 2020 Nov 13:1-7. Epub 2020 Nov 13.

3Department of Radiology, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.

Objective: Superselective pseudocontinuous arterial spin labeling (ss-pCASL) is an MRI technique in which individual vessels are labeled to trace their perfusion territories. In this study, the authors assessed its merit in defining feeding vessels and gauging preoperative embolization feasibility for patients with meningioma, using digital subtraction angiography (DSA) as the reference method.

Methods: Thirty-one consecutive patients with meningiomas were prospectively recruited, each undergoing DSA (and embolization, if feasible) before resection. All ss-pCASL imaging studies were performed 1 day prior to DSA. Two neuroradiologists independently reviewed ss-pCASL images, rating the contribution of each labeled vessel to tumor blood supply as none, minor, or major. Two neuroradiologists also gauged the feasibility of embolization in each patient, based on ss-pCASL images. Interobserver and intermodality agreement were determined using Cohen's kappa statistic. The diagnostic performance of ss-pCASL was assessed in terms of discerning tumor blood supply and the potential for embolization.

Results: Interobserver agreement in the rating of blood supply by ss-pCASL was very good (κ = 0.817, 95% CI 0.771-0.863), and intermodality agreement (consensus ss-pCASL readings vs DSA findings) was good (κ = 0.688, 95% CI 0.632-0.744). In delineating tumor blood supply, ss-pCASL showed high sensitivity (87.1%) and specificity (87.2%). The positive and negative predictive values for embolization feasibility were 85.2% and 100%, respectively.

Conclusions: In patients with meningiomas, feeding vessels are reliably predicted by ss-pCASL. This noninvasive approach, involving no iodinated contrast or radiation exposure, is particularly beneficial if there are no prospects of embolization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.7.JNS201915DOI Listing
November 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2020.0011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817637PMC
February 2021

Association of carotid and intracranial stenosis with Alzheimer's disease biomarkers.

Alzheimers Res Ther 2020 09 10;12(1):106. Epub 2020 Sep 10.

Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea.

Background: To clarify whether atherosclerosis of the carotid and intracranial arteries is related to Alzheimer's disease (AD) pathology in vivo, we investigated the associations of carotid and intracranial artery stenosis with cerebral beta-amyloid (Aβ) deposition and neurodegeneration in middle- and old-aged individuals. Given different variations of the pathologies between cognitive groups, we focused separately on cognitively normal (CN) and cognitively impaired (CI) groups.

Methods: A total of 281 CN and 199 CI (mild cognitive impairment and AD dementia) subjects underwent comprehensive clinical assessment, [C] Pittsburgh compound B-positron emission tomography, and magnetic resonance (MR) imaging including MR angiography. We evaluated extracranial carotid and intracranial arteries for the overall presence, severity (i.e., number and degree of narrowing), and location of stenosis.

Results: We found no associations between carotid and intracranial artery stenosis and cerebral Aβ burden in either the CN or the CI group. In terms of neurodegeneration, exploratory univariable analyses showed associations between the presence and severity of stenosis and regional neurodegeneration biomarkers (i.e., reduced hippocampal volume [HV] and cortical thickness in the AD-signature regions) in both the CN and CI groups. In confirmatory multivariable analyses controlling for demographic covariates and diagnosis, the association between number of stenotic intracranial arteries ≥ 2 and reduced HV in the CI group remained significant.

Conclusions: Neither carotid nor intracranial artery stenosis appears to be associated with brain Aβ burden, while intracranial artery stenosis is related to amyloid-independent neurodegeneration, particularly hippocampal atrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-020-00675-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488394PMC
September 2020

Rapid three-dimensional steady-state chemical exchange saturation transfer magnetic resonance imaging.

Magn Reson Med 2021 03 27;85(3):1209-1221. Epub 2020 Aug 27.

Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Republic of Korea.

Purpose: To make clinically feasible whole-brain chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) by enhancing imaging efficiency.

Methods: A novel, whole-brain three-dimensional (3D) steady-state CEST MRI method was introduced by utilizing a time-efficient, fat-suppressed excitation followed by rapid, segmented 3D echo-planar-imaging with incoherent undersampling in k-ω space. Missing signals and CEST-specific spectral images were then jointly estimated directly from incomplete measurements using model-based reconstruction and robust spectral analysis. In vivo studies were performed at 3T both retrospectively (using a fully sampled reference) and prospectively to validate the effectiveness of the proposed method in patients with brain cancer.

Results: In retrospective studies, the proposed method exhibits superior accuracies to existing methods in estimating images, z-spectra, and APTw relative to the reference. In prospective patient studies, compared with existing methods, the proposed method is statistically significantly different in contrast-to-noise ratio of the APTw contrast between tumor and normal appearing white matter (NAWM) and amide proton transfer weighted contrast (p < 0.05) while not being significantly different in signal-to-noise ratio in an NAWM region.

Conclusions: We successfully demonstrated that it is feasible to perform whole-brain CEST MRI roughly within 4 minutes for patients with brain cancer. It is expected that the proposed method widens clinical utilities of CEST MRI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28487DOI Listing
March 2021

Prediction of Amyloid Positivity in Mild Cognitive Impairment Using Fully Automated Brain Segmentation Software.

Neuropsychiatr Dis Treat 2020 22;16:1745-1754. Epub 2020 Jul 22.

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

Objective: To assess the predictive ability of regional volume information provided by fully automated brain segmentation software for cerebral amyloid positivity in mild cognitive impairment (MCI).

Methods: This study included 130 subjects with amnestic MCI who participated in the Korean brain aging study of early diagnosis and prediction of Alzheimer's disease, an ongoing prospective cohort. All participants underwent comprehensive clinical assessment as well as C-labeled Pittsburgh compound PET/MRI scans. The predictive ability of volumetric results provided by automated brain segmentation software was evaluated using binary logistic regression and receiver operating characteristic curve analysis.

Results: Subjects were divided into two groups: one with Aβ deposition (58 subjects) and one without Aβ deposition (72 subjects). Among the varied volumetric information provided, the hippocampal volume percentage of intracranial volume (%HC/ICV), normative percentiles of hippocampal volume (HC), and gray matter volume were associated with amyloid-β (Aβ) positivity (all < 0.01). Multivariate analyses revealed that both %HC/ICV and HC were independent significant predictors of Aβ positivity (all < 0.001). In addition, prediction scores derived from %HC/ICV with age and HC showed moderate accuracy in predicting Aβ positivity in MCI subjects (the areas under the curve: 0.739 and 0.723, respectively).

Conclusion: Relative hippocampal volume measures provided by automated brain segmentation software can be useful for screening cerebral Aβ positivity in clinical practice for patients with amnestic MCI. The information may also help clinicians interpret structural MRI to predict outcomes and determine early intervention for delaying the progression to Alzheimer's disease dementia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/NDT.S252293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383107PMC
July 2020

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.

Korean J Radiol 2021 01 11;22(1):118-130. Epub 2020 Aug 11.

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

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 K and v 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. K 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 K values in mTBI patients than in controls). The Mann-Whitney U test and Spearman rank correlation test were performed to compare the mean K and v between the two groups and correlate K and v 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 K in the bilateral cerebral cortex was significantly higher in mTBI patients than in controls ( = 0.042). The mean v values in the bilateral cerebellar WM and brainstem were significantly lower in mTBI patients than in controls ( = 0.009 and = 0.011, respectively). The mean K 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 ( = 0.041).

Conclusion: BBB disruption, as reflected by the increased K and decreased v values from the Patlak model, was observed throughout the bilateral cerebral cortex, bilateral cerebellar WM, and brainstem in mTBI patients with PCS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2020.0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772380PMC
January 2021

Serum albumin and beta-amyloid deposition in the human brain.

Neurology 2020 08 20;95(7):e815-e826. Epub 2020 Jul 20.

From the Department of Neuropsychiatry (J.W.K.), Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si, Gyeonggi-do; Department of Psychiatry (J.W.K.), Hallym University College of Medicine, Chuncheon, Gangwan-do; Institute of Human Behavioral Medicine (M.S.B., D.Y., D.Y.L.), Medical Research Center Seoul National University; Departments of Neuropsychiatry (J.H.L., D.Y.L.) and Radiology (K.M.K., C.-H.S.), Seoul National University Hospital; Department of Psychiatry (S.Y.J.), Chungnam National University Hospital, Daejeon; Sanggye Paik Hospital (B.K.S.), Department of Psychiatry, Inje University College of Medicine; Departments of Neuropsychiatry (J.-Y.L.) and Nuclear Medicine (S.A.S., Y.K.K.), SMG-SNU Boramae Medical Center; and Department of Psychiatry (J.-Y.L., D.Y.L.), Seoul National University College of Medicine, Republic of Korea.

Objectives: To investigate the relationships of serum albumin with in vivo Alzheimer disease (AD) pathologies, including cerebral β-amyloid (Aβ) protein deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH), in the human brain.

Methods: A total of 396 older adults without dementia underwent comprehensive clinical assessments, measurement of serum albumin level, and multimodal brain imaging, including [C] Pittsburgh compound B-PET, F-fluorodeoxyglucose-PET, and MRI. Serum albumin was categorized as follows: <4.4 g/dL (low albumin), 4.4 to 4.5 g/dL (middle albumin), and >4.5 g/dL (high albumin; used as a reference category). Aβ positivity, AD-signature region cerebral glucose metabolism (AD-CM), AD-signature region cortical thickness (AD-CT), and WMH volume were used as outcome measures.

Results: Serum albumin level (as a continuous variable) was inversely associated with Aβ deposition and Aβ positivity. The low albumin group showed a significantly higher Aβ positivity rate compared to the high albumin group (odds ratio 3.40, 95% confidence interval 1.67-6.92, = 0.001), while the middle albumin group showed no difference (odds ratio 1.74, 95% confidence interval 0.80-3.77, = 0.162). Neither serum albumin level (as a continuous variable) nor albumin categories were related to AD-CM, AD-CT, or WMH volume.

Conclusions: Low serum albumin may increase the risk of AD dementia by elevating amyloid accumulation. In terms of AD prevention, more attention needs to be paid to avoid a low serum albumin level, even within the clinical normal range, by clinicians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000010005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605506PMC
August 2020

Serum Uric Acid, Alzheimer-Related Brain Changes, and Cognitive Impairment.

Front Aging Neurosci 2020 5;12:160. Epub 2020 Jun 5.

Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, South Korea.

Background: Despite known associations of lower serum uric acid (UA) with Alzheimer's disease (AD) dementia or AD-related cognitive impairment, little is known regarding the underlying patho-mechanisms. We aimed to examine the relationships of serum UA with in vivo AD pathologies including cerebral beta-amyloid (Aβ) and tau deposition, AD-signature region cerebral glucose metabolism (AD-CM), and white matter hyperintensities (WMH). We also investigated the association between serum UA and cognitive performance, and then assessed whether such an association is mediated by the brain pathologies.

Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessments, measurement of serum UA level, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging scans. Mini-Mental State Examination (MMSE) and word list recall (WLR) test scores were used to measure cognitive performance.

Results: Serum UA level was significantly associated with AD-CM, but not with Aβ deposition, tau deposition, or WMH volume. Serum UA levels also had significant association with WLR and marginal association with MMSE; such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a mediating effect.

Conclusion: The findings of the present study indicate that there is an association of low serum UA with AD-related cerebral hypometabolism, and whether this represents a causal relationship remains to be determined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2020.00160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291838PMC
June 2020

Multiparity, Brain Atrophy, and Cognitive Decline.

Front Aging Neurosci 2020 3;12:159. Epub 2020 Jun 3.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.

Background: Multiparity - grand multiparity (i.e., five or more childbirths) in particular - has been reported to have an association with increased risk of Alzheimer's disease (AD) dementia or related cognitive decline in women. However, the pathological links underlying this relationship are still unknown. This study was conducted to examine the relationships of multiparity with cerebral amyloid-beta (Aβ) deposition, brain atrophy, and white matter hyperintensities (WMHs).

Methods: In this study, total of 237 older women with 148 cognitively normal and 89 mild cognitive impairment from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) were included. Participants underwent clinical and neuropsychological assessments in addition to C-labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. The associations of parity with Aβ deposition, hippocampal volume, cortical volume, WMH volume and mini-mental status examination (MMSE) score were examined.

Results: Participants with grand multiparity showed significantly reduced adjusted hippocampal volume, spatial pattern of atrophy for recognition of AD volume and spatial pattern of atrophy for recognition of brain aging volume even after controlling for potential confounders. Furthermore, MMSE score was also significantly lower in this group. In contrast, grand multiparity did not show any association with global Aβ retention, Aβ positivity rate, or WMH volume, regardless of covariates.

Conclusion: Our findings suggest that grand multiparity contributes to cognitive decline or increased dementia risk in older women by aggravating amyloid-independent hippocampal or cortical atrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2020.00159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291884PMC
June 2020

Diagnostic Accuracy and Confidence of [18F] FDG PET/MRI in comparison with PET or MRI alone in Head and Neck Cancer.

Sci Rep 2020 06 11;10(1):9490. Epub 2020 Jun 11.

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

The usefulness of PET/MRI in head and neck malignancy has not been fully elucidated. The purpose of our study was to evaluate the diagnostic accuracy and confidence of PET/MRI in comparison with PET or MRI alone. This study included 73 consecutive patients who underwent [18F] FDG PET/MRI in head and neck under the suspicion of malignancy. A neuroradiologist and a nuclear medicine specialist reviewed MRI and PET images, respectively and independently, followed by a consensus review of PET/MRI one month later. For 134 lesions, accuracy and confidence were compared among PET, MRI, and PET/MRI. For lesion base, PET/MRI had a sensitivity of 85.7%, a specificity of 89.1%, a PPV of 89.6%, a negative predictive value of 85.1%, and an accuracy of 87.3%. AUCs of PET/MRI per lesion (0.926) and per patient (0.934) for diagnosing malignancy were higher than PET (0.847 and 0.747, respectively) or MRI (0.836 and 0.798, respectively) alone (P < 0.05). More than 80% of the cases (111/134) showed diagnostic concordance between PET and MRI. PPV of PET/MRI was higher in malignant concordant cases (93.2%, 55/59) than in discordant cases (62.5%, 5/8) (p = 0.040). Confident scoring rate in malignant concordant cases was higher on PET/MRI (96.6%, 57/59) than on MRI (76.3%, 45/59) (p = 0.003). In conclusion, compared with PET or MRI alone, PET/MRI presents better diagnostic performance in accuracy and confidence for diagnosis of malignancy. PET/MRI is useful in patients with head and neck cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-66506-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289810PMC
June 2020

Prognostic Value of Dynamic Contrast-Enhanced MRI-Derived Pharmacokinetic Variables in Glioblastoma Patients: Analysis of Contrast-Enhancing Lesions and Non-Enhancing T2 High-Signal Intensity Lesions.

Korean J Radiol 2020 06;21(6):707-716

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

Objective: To evaluate pharmacokinetic variables from contrast-enhancing lesions (CELs) and non-enhancing T2 high signal intensity lesions (NE-T2HSILs) on dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for predicting progression-free survival (PFS) in glioblastoma (GBM) patients.

Materials And Methods: Sixty-four GBM patients who had undergone preoperative DCE MR imaging and received standard treatment were retrospectively included. We analyzed the pharmacokinetic variables of the volume transfer constant (Ktrans) and volume fraction of extravascular extracellular space within the CEL and NE-T2HSIL of the entire tumor. Univariate and multivariate Cox regression analyses were performed using preoperative clinical characteristics, pharmacokinetic variables of DCE MR imaging, and postoperative molecular biomarkers to predict PFS.

Results: The increased mean Ktrans of the CEL, increased 95th percentile Ktrans of the CELs, and absence of methylated O⁶-methylguanine-DNA methyltransferase promoter were relevant adverse variables for PFS in the univariate analysis ( = 0.041, = 0.032, and = 0.083, respectively). The Kaplan-Meier survival curves demonstrated that PFS was significantly shorter in patients with a mean Ktrans of the CEL > 0.068 and 95th percentile Ktrans of the CEL>0.223 (log-rank = 0.038 and = 0.041, respectively). However, only mean Ktrans of the CEL was significantly associated with PFS ( = 0.024; hazard ratio, 553.08; 95% confidence interval, 2.27-134756.74) in the multivariate Cox proportional hazard analysis. None of the pharmacokinetic variables from NE-T2HSILs were significantly related to PFS.

Conclusion: Among the pharmacokinetic variables extracted from CELs and NE-T2HSILs on preoperative DCE MR imaging, the mean Ktrans of CELs exhibits potential as a useful imaging predictor of PFS in GBM patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2019.0629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231611PMC
June 2020

Added Value of Computed Tomography to Ultrasonography for Assessing LN Metastasis in Preoperative Patients with Thyroid Cancer: Node-By-Node Correlation.

Cancers (Basel) 2020 May 8;12(5). Epub 2020 May 8.

Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea.

Diagnostic accuracy of US in the evaluation of lymph node (LN) metastasis for thyroid cancer patients is limited. We investigated the value of CT added to US for characterizing LNs in preoperative thyroid cancer patients by node-by-node correlation. A total of 225 primary thyroid cancer patients who underwent LN biopsy were included. Based on node-by-node correlation, 274 LNs were classified into probably benign, indeterminate, and suspicious categories on US, CT, and combined US/CT. Malignancy risks were calculated for each category and were compared between US/CT concordant and discordant cases. On US, CT, and combined US/CT, malignancy risks were 1.7%, 8.7%, and 0% in the probably benign category, 22.4%, 5.9%, and 8.0% in the indeterminate category, and 77.2%, 82.0%, and 75.6% in the suspicious category, respectively. Malignancy risk of the concordant suspicious category was higher than that of the discordant suspicious category (84.7% vs. 43.2%, < 0.001). The addition of CT helped correctly detect additional metastasis in 16.4% of the US indeterminate LNs and in 1.7% of the US probably benign LNs. CT may complement US for LN characterization in thyroid cancer patients by suggesting the diagnostic confidence level for the suspicious category and helping correctly detect metastasis in US indeterminate LNs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12051190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281101PMC
May 2020

Sex-Specific Association of Lifetime Body Mass Index with Alzheimer's Disease Neuroimaging Biomarkers.

J Alzheimers Dis 2020 ;75(3):767-777

Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea.

Background: Although recent studies indicate that the relationship between body mass index (BMI) and Alzheimer's disease (AD) may differ by both sex and age of BMI measurement, little information is available on sex- or age-specific associations between BMI and AD neuropathologies.

Objective: To examined whether sex-specific BMIs measured at different life-stages (in early adulthood, midlife, and late life) were associated with cerebral amyloid-β (Aβ) deposition and AD-signature region cortical thickness (AD-CT) in cognitively normal (CN) older adults.

Methods: A total of 212 CN subjects aged 60-90 years (females 108, males 104), who participated in the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study, were included. All participants underwent comprehensive clinical and neuropsychological assessments, [11C] Pittsburgh Compound B positron emission tomography, and brain magnetic resonance imaging. BMIs at different life stages were calculated. Multiple regression analyses were performed separately for either sex.

Results: In males, lower early adulthood or midlife BMI was associated with greater cerebral Aβ deposition, but late life BMI was not. Lower midlife BMI was associated with reduced AD-CT, but the BMI in early adulthood and late life was not. In females, no significant association was observed between any lifetime BMI and Aβ deposition or AD-CT.

Conclusion: Our results support a male-specific association between BMI prior to late life, and in vivo AD pathologies. Avoiding underweight status early in life may be important to prevent AD dementia in males, but not females.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-191216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369081PMC
May 2021

Ultrasonographic Indeterminate Lymph Nodes in Preoperative Thyroid Cancer Patients: Malignancy Risk and Ultrasonographic Findings Predictive of Malignancy.

Korean J Radiol 2020 05;21(5):598-604

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

Objective: Proper management of lymph nodes (LNs) with ultrasonographic (US) indeterminate features in thyroid cancer patients remains elusive. We aimed to evaluate the malignancy risk and US findings predictive of malignancy for US indeterminate LNs in preoperative thyroid cancer patients through node-by-node correlation.

Materials And Methods: A total of 348 LNs in 284 thyroid cancer patients, who underwent fine-needle aspiration or core-needle biopsy between December 2006 and June 2015, were included. We determined the malignancy risks for US probably benign, indeterminate, and suspicious categories. For US indeterminate LNs, which had neither echogenic hilum nor hilar vascularity in the absence of any suspicious finding, US findings were compared between benign and metastatic LNs using Mann-Whitney U test and Fisher's exact test.

Results: US imaging diagnoses were probably benign in 20.7% (n = 72) cases, indeterminate in 23.6% (n = 82), and suspicious in 55.7% (n = 194). Malignancy risk of US indeterminate LNs (19.5% [16/82]) differed from those of the US probably benign (2.8% [2/72]) ( = 0.002) and US suspicious LNs (78.4% [152/194]) ( < 0.001). Among US indeterminate LNs, there were no significant differences in short, long, and long-to-short diameter (L/S) ratios between benign and metastatic LNs (3.9 vs. 3.8 mm, = 0.619; 7.3 vs. 7.3 mm, = 0.590; 1.9 vs. 1.9, = 0.652).

Conclusion: US indeterminate LNs were frequently encountered during preoperative evaluation and had intermediate malignancy risk. Given the lack of discriminative power of size criteria and L/S ratio, clinical factors such as surgical strategy and node size should be considered for proper triage of US indeterminate LNs in thyroid cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2019.0755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183832PMC
May 2020

Midlife Lifestyle Activities Moderate APOE ε4 Effect on Alzheimer's Disease Pathologies.

Front Aging Neurosci 2020 27;12:42. Epub 2020 Feb 27.

Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.

This study aimed to investigate whether the midlife cognitive activity and physical activity moderate the relationship between apolipoprotein Eε4 (APOE4) and Alzheimer's disease (AD) pathologies. In total, 287 non-demented older adults (mean age 72 years) from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer's disease cohort were included. Participants underwent a comprehensive clinical assessment including the evaluation for midlife CA and physical activity, [C]-Pittsburgh-Compound-B-positron emission tomography (PET), [F]-fluorodeoxyglucose PET, structural magnetic resonance imaging (MRI), and APOE genotyping. We used linear regression and regression-based mediated-moderation models for statistical analyses. Neither midlife cognitive activity nor physical activity moderated the effect of APOE4 on β-amyloid (Aβ) retention itself. Midlife cognitive activity significantly moderated the effect of APOE4 on hippocampal volume [ (SE) = - 627.580 (252.327), = -2.488, = 0.014]: APOE4 carriers had smaller hippocampal volume than non-carriers at relatively high cognitive activity state ( = 0.004), but not at relatively low cognitive activity condition ( = 0.937). Midlife physical activity significantly moderated the effect of Aβ retention, which was closely related to APOE4, on AD-signature region cerebral glucose metabolism [AD-CM; (SE) = 0.004 (0.002), = 2.030, = 0.043]: higher Aβ accumulation was associated with lower AD-CM in relatively low physical activity condition ( < 0.001), whereas no such association was observed in relatively high physical activity state ( = 0.791). The findings suggest that high midlife cognitive activity may accelerate hippocampal atrophy induced by APOE4, whereas high midlife physical activity may delay AD-related cerebral hypometabolism by weakening the influence of APOE4-associated Aβ retention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2020.00042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093017PMC
February 2020
-->