Primary epithelioid inflammatory myofibroblastic sarcoma of the brain with EML4::ALK fusion mimicking intra-axial glioma: a case report and brief literature review.

An aggressive subtype of inflammatory myofibroblastic tumor, epithelioid inflammatory myofibroblastic sarcoma occurs primarily inside the abdominal cavity, followed by a pulmonary localization. Most harbor anaplastic lymphoma kinase (ALK) gene rearrangements, with RANBP2 and RRBP1 among the well-documented fusion partners. We report the second case of primary epithelioid inflammatory myofibroblastic sarcoma of the brain, with a well-known EML4::ALK fusion. The case is notable for its intra-axial presentation that clinico-radiologically mimicked glioma.

MRI Scoring Systems for Predicting Isocitrate Dehydrogenase Mutation and Chromosome 1p/19q Codeletion in Adult-type Diffuse Glioma Lacking Contrast Enhancement.

Background According to 2021 World Health Organization criteria, adult-type diffuse gliomas include glioblastoma, isocitrate dehydrogenase (IDH)-wildtype; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and astrocytoma, IDH-mutant, even when contrast enhancement is lacking. Purpose To develop and validate simple scoring systems for predicting IDH and subsequent 1p/19q codeletion status in gliomas without contrast enhancement using standard clinical MRI sequences. Materials and Methods This retrospective study included adult-type diffuse gliomas lacking contrast at contrast-enhanced MRI from two tertiary referral hospitals between January 2012 and April 2022 with diagnoses confirmed at pathology. IDH status was predicted primarily by using T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, followed by 1p/19q codeletion prediction. A visual rating of MRI features, apparent diffusion coefficient (ADC) ratio, and relative cerebral blood volume was measured. Scoring systems were developed through univariable and multivariable logistic regressions and underwent calibration and discrimination, including internal and external validation. Results For the internal validation cohort, 237 patients were included (mean age, 44.4 years ± 14.4 [SD]; 136 male patients; 193 patients in IDH prediction and 163 patients in 1p/19q prediction). For the external validation cohort, 35 patients were included (46.1 years ± 15.3; 20 male patients; 28 patients in IDH prediction and 24 patients in 1p/19q prediction). The T2-FLAIR mismatch sign demonstrated 100% specificity and 100% positive predictive value for IDH mutation. IDH status prediction scoring system for tumors without mismatch sign included age, ADC ratio, and morphologic characteristics, whereas 1p/19q codeletion prediction for IDH-mutant gliomas included ADC ratio, cortical involvement, and mismatch sign. For IDH status and 1p/19q codeletion prediction, bootstrap-corrected areas under the receiver operating characteristic curve were 0.86 (95% CI: 0.81, 0.90) and 0.73 (95% CI: 0.65, 0.81), respectively, whereas at external validation they were 0.99 (95% CI: 0.98, 1.0) and 0.88 (95% CI: 0.63, 1.0). Conclusion The T2-FLAIR mismatch sign and scoring systems using standard clinical MRI predicted IDH and 1p/19q codeletion status in gliomas lacking contrast enhancement. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Badve and Hodges in this issue.

Plasma Leptin and Alzheimer Protein Pathologies Among Older Adults.

Importance: Many epidemiologic studies have suggested that low levels of plasma leptin, a major adipokine, are associated with increased risk of Alzheimer disease (AD) dementia and cognitive decline. Nevertheless, the mechanistic pathway linking plasma leptin and AD-related cognitive decline is not yet fully understood. Objective: To examine the association of plasma leptin levels with in vivo AD pathologies, including amyloid-beta (Aß) and tau deposition, through both cross-sectional and longitudinal approaches among cognitively unimpaired older adults. Design, Setting, and Participants: This was a longitudinal cohort study from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease. Data were collected from January 1, 2014, to December 31, 2020, and data were analyzed from July 11 to September 6, 2022. The study included a total of 208 cognitively unimpaired participants who underwent baseline positron emission tomography (PET) scans for brain Aß deposition. For longitudinal analyses, 192 participants who completed both baseline and 2-year follow-up PET scans for brain Aß deposition were included. Exposure: Plasma leptin levels as assessed by enzyme-linked immunosorbent assay. Main Outcomes and Measures: Baseline levels and longitudinal changes of global Aß and AD-signature region tau deposition measured by PET scans. Results: Among the 208 participants, the mean (SD) age was 66.0 (11.3) years, 114 were women (54.8%), and 37 were apolipoprotein E ε4 carriers (17.8%). Lower plasma leptin levels had a significant cross-sectional association with greater brain Aß deposition (ß = -0.04; 95% CI, -0.09 to 0.00; P = .046), while there was no significant association between plasma leptin levels and tau deposition (ß = -0.02; 95% CI, -0.05 to 0.02; P = .41). In contrast, longitudinal analyses revealed that there was a significant association between lower baseline leptin levels and greater increase of tau deposition over 2 years (ß = -0.06; 95% CI, -0.11 to -0.01; P = .03), whereas plasma leptin levels did not have a significant association with longitudinal change of Aß deposition (ß = 0.006; 95% CI, 0.00-0.02; P = .27). Conclusions and Relevance: The present findings suggest that plasma leptin may be protective for the development or progression of AD pathology, including both Aß and tau deposition.

Association between brain amyloid deposition and longitudinal changes of white matter hyperintensities.

BACKGROUND: Growing evidence suggests that not only cerebrovascular disease but also Alzheimer's disease (AD) pathological process itself cause cerebral white matter degeneration, resulting in white matter hyperintensities (WMHs). Some preclinical evidence also indicates that white matter degeneration may precede or affect the development of AD pathology. This study aimed to clarify the direction of influence between in vivo AD pathologies, particularly beta-amyloid (Aß) and tau deposition, and WMHs through longitudinal approach. METHODS: Total 282 older adults including cognitively normal and cognitively impaired individuals were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B PET for measuring Aß deposition, [18F] AV-1451 PET for measuring tau deposition, and MRI scans with fluid-attenuated inversion recovery image for measuring WMH volume. The relationships between Aß or tau deposition and WMH volume were examined using multiple linear regression analysis. In this analysis, baseline Aß or tau were used as independent variables, and change of WMH volume over 2 years was used as dependent variable to examine the effect of AD pathology on increase of WMH volume. Additionally, we set baseline WMH volume as independent variable and longitudinal change of Aß or tau deposition for 2 years as dependent variables to investigate whether WMH volume could precede AD pathologies. RESULTS: Baseline Aß deposition, but not tau deposition, had significant positive association with longitudinal change of WMH volume over 2 years. Baseline WMH volume was not related with any of longitudinal change of Aß or tau deposition for 2 years. We also found a significant interaction effect between baseline Aß deposition and sex on longitudinal change of WMH volume. Subsequent subgroup analyses showed that high baseline Aß deposition was associated with increase of WMH volume over 2 years in female, but not in male. CONCLUSIONS: Our findings suggest that Aß deposition accelerates cerebral WMHs, particularly in female, whereas white matter degeneration appears not influence on longitudinal Aß increase. The results also did not support any direction of influence between tau deposition and WMHs.

Dynamic Contrast-enhanced MRI Quantification of Altered Vascular Permeability in Autoimmune Encephalitis.

Background Blood-brain barrier (BBB) permeability change is a possible pathologic mechanism of autoimmune encephalitis. Purpose To evaluate the change in BBB permeability in patients with autoimmune encephalitis as compared with healthy controls by using dynamic contrast-enhanced (DCE) MRI and to explore its predictive value for treatment response in patients. Materials and Methods This single-center retrospective study included consecutive patients with probable or possible autoimmune encephalitis and healthy controls who underwent DCE MRI between April 2020 and May 2021. Automatic volumetric segmentation was performed on three-dimensional T1-weighted images, and volume transfer constant (Ktrans) values were calculated at encephalitis-associated brain regions. Ktrans values were compared between the patients and controls, with adjustment for age and sex with use of a nonparametric approach. The Wilcoxon rank sum test was performed to compare Ktrans values of the good (improvement in modified Rankin Scale [mRS] score of at least two points or achievement of an mRS score of ≤2) and poor (improvement in mRS score of less than two points and achievement of an mRS score >2) treatment response groups among the patients. Results Thirty-eight patients with autoimmune encephalitis (median age, 38 years [IQR, 29-59 years]; 20 [53%] female) and 17 controls (median age, 71 years [IQR, 63-77 years]; 12 [71%] female) were included. All brain regions showed higher Ktrans values in patients as compared with controls (P < .001). The median difference in Ktrans between the patients and controls was largest in the right parahippocampal gyrus (25.1 × 10-4 min-1 [95% CI: 17.6, 43.4]). Among patients, the poor treatment response group had higher baseline Ktrans values in both cerebellar cortices (P = .03), the left cerebellar cortex (P = .02), right cerebellar cortex (P = .045), left cerebral cortex (P = .045), and left postcentral gyrus (P = .03) than the good treatment response group. Conclusion DCE MRI demonstrated that BBB permeability was increased in all brain regions in patients with autoimmune encephalitis as compared with controls, and baseline Ktrans values were higher in patients with poor treatment response in the cerebellar cortex, left cerebral cortex, and left postcentral gyrus as compared with the good response group. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Filippi and Rocca in this issue.

Added value of dynamic contrast-enhanced MR imaging in deep learning-based prediction of local recurrence in grade 4 adult-type diffuse gliomas patients.

Local recurrences in patients with grade 4 adult-type diffuse gliomas mostly occur within residual non-enhancing T2 hyperintensity areas after surgical resection. Unfortunately, it is challenging to distinguish non-enhancing tumors from edema in the non-enhancing T2 hyperintensity areas using conventional MRI alone. Quantitative DCE MRI parameters such as Ktrans and Ve convey permeability information of glioblastomas that cannot be provided by conventional MRI. We used the publicly available nnU-Net to train a deep learning model that incorporated both conventional and DCE MRI to detect the subtle difference in vessel leakiness due to neoangiogenesis between the non-recurrence area and the local recurrence area, which contains a higher proportion of high-grade glioma cells. We found that the addition of Ve doubled the sensitivity while nonsignificantly decreasing the specificity for prediction of local recurrence in glioblastomas, which implies that the combined model may result in fewer missed cases of local recurrence. The deep learning model predictive of local recurrence may enable risk-adapted radiotherapy planning in patients with grade 4 adult-type diffuse gliomas.

White matter integrity is associated with cognition and amyloid burden in older adult Koreans along the Alzheimer's disease continuum.

BACKGROUND: White matter (WM) microstructural changes in the hippocampal cingulum bundle (CBH) in Alzheimer's disease (AD) have been described in cohorts of largely European ancestry but are lacking in other populations. METHODS: We assessed the relationship between CBH WM integrity and cognition or amyloid burden in 505 Korean older adults aged ≥ 55 years, including 276 cognitively normal older adults (CN), 142 with mild cognitive impairment (MCI), and 87 AD patients, recruited as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) at Seoul National University. RESULTS: Compared to CN, AD and MCI subjects showed significantly higher RD, MD, and AxD values (all p-values < 0.001) and significantly lower FA values (left p ≤ 0.002, right p ≤ 0.015) after Bonferroni adjustment for multiple comparisons. Most tests of cognition and mood (p < 0.001) as well as higher medial temporal amyloid burden (p < 0.001) were associated with poorer WM integrity in the CBH after Bonferroni adjustment. CONCLUSION: These findings are consistent with patterns of WM microstructural damage previously reported in non-Hispanic White (NHW) MCI/AD cohorts, reinforcing existing evidence from predominantly NHW cohort studies.

Deep learning based on dynamic susceptibility contrast MR imaging for prediction of local progression in adult-type diffuse glioma (grade 4).

Adult-type diffuse glioma (grade 4) has infiltrating nature, and therefore local progression is likely to occur within surrounding non-enhancing T2 hyperintense areas even after gross total resection of contrast-enhancing lesions. Cerebral blood volume (CBV) obtained from dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) is a parameter that is well-known to be a surrogate marker of both histologic and angiographic vascularity in tumors. We built two nnU-Net deep learning models for prediction of early local progression in adult-type diffuse glioma (grade 4), one using conventional MRI alone and one using multiparametric MRI, including conventional MRI and DSC-PWI. Local progression areas were annotated in a non-enhancing T2 hyperintense lesion on preoperative T2 FLAIR images, using the follow-up contrast-enhanced (CE) T1-weighted (T1W) images as the reference standard. The sensitivity was doubled with the addition of nCBV (80% vs. 40%, P = 0.02) while the specificity was decreased nonsignificantly (29% vs. 48%, P = 0.39), suggesting that fewer cases of early local progression would be missed with the addition of nCBV. While the diagnostic performance of CBV model is still poor and needs improving, the multiparametric deep learning model, which presumably learned from the subtle difference in vascularity between early local progression and non-progression voxels within perilesional T2 hyperintensity, may facilitate risk-adapted radiotherapy planning in adult-type diffuse glioma (grade 4) patients.

Validation of Ultrasound and Computed Tomography-Based Risk Stratification System and Biopsy Criteria for Cervical Lymph Nodes in Preoperative Patients With Thyroid Cancer.

OBJECTIVE: This study aimed to validate the risk stratification system (RSS) and biopsy criteria for cervical lymph nodes (LNs) proposed by the Korean Society of Thyroid Radiology (KSThR). MATERIALS AND METHODS: This retrospective study included a consecutive series of preoperative patients with thyroid cancer who underwent LN biopsy, ultrasound (US), and computed tomography (CT) between December 2006 and June 2015. LNs were categorized as probably benign, indeterminate, or suspicious according to the current US- and CT-based RSS and the size thresholds for cervical LN biopsy as suggested by the KSThR. The diagnostic performance and unnecessary biopsy rates were calculated. RESULTS: A total of 277 LNs (53.1% metastatic) in 228 patients (mean age ± standard deviation, 47.4 years ± 14) were analyzed. In US, the malignancy risks were significantly different among the three categories (all P < 0.001); however, CT-detected probably benign and indeterminate LNs showed similarly low malignancy risks (P = 0.468). The combined US + CT criteria stratified the malignancy risks among the three categories (all P < 0.001) and reduced the proportion of indeterminate LNs (from 20.6% to 14.4%) and the malignancy risk in the indeterminate LNs (from 31.6% to 12.5%) compared with US alone. In all image-based classifications, nodal size did not affect the malignancy risks (short diameter [SD] ≤ 5 mm LNs vs. SD > 5 mm LNs, P ≥ 0.177). The criteria covering only suspicious LNs showed higher specificity and lower unnecessary biopsy rates than the current criteria, while maintaining sensitivity in all imaging modalities. CONCLUSION: Integrative evaluation of US and CT helps in reducing the proportion of indeterminate LNs and the malignancy risk among them. Nodal size did not affect the malignancy risk of LNs, and the addition of indeterminate LNs to biopsy candidates did not have an advantage in detecting LN metastases in all imaging modalities.

Deep learning-based reconstruction for acceleration of lumbar spine MRI: a prospective comparison with standard MRI.

OBJECTIVE: To compare the image quality and diagnostic performance between standard turbo spin-echo MRI and accelerated MRI with deep learning (DL)-based image reconstruction for degenerative lumbar spine diseases. MATERIALS AND METHODS: Fifty patients who underwent both the standard and accelerated lumbar MRIs at a 1.5-T scanner for degenerative lumbar spine diseases were prospectively enrolled. DL reconstruction algorithm generated coarse (DL_coarse) and fine (DL_fine) images from the accelerated protocol. Image quality was quantitatively assessed in terms of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) and qualitatively assessed using five-point visual scoring systems. The sensitivity and specificity of four radiologists for the diagnosis of degenerative diseases in both protocols were compared. RESULTS: The accelerated protocol reduced the average MRI acquisition time by 32.3% as compared to the standard protocol. As compared with standard images, DL_coarse and DL_fine showed significantly higher SNRs on T1-weighted images (T1WI; both p < .001) and T2-weighted images (T2WI; p = .002 and p < 0.001), higher CNRs on T1WI (both p < 0.001), and similar CNRs on T2WI (p = .49 and p = .27). The average radiologist assessment of overall image quality for DL_coarse and DL_fine was higher on sagittal T1WI (p = .04 and p < .001) and axial T2WI (p = .006 and p = .01) and similar on sagittal T2WI (p = .90 and p = .91). Both DL_coarse and DL_fine had better image quality of cauda equina and paraspinal muscles on axial T2WI (both p = .04 for cauda equina; p = .008 and p = .002 for paraspinal muscles). Differences in sensitivity and specificity for the detection of central canal stenosis and neural foraminal stenosis between standard and DL-reconstructed images were all statistically nonsignificant (p ≥ 0.05). CONCLUSION: DL-based protocol reduced MRI acquisition time without degrading image quality and diagnostic performance of readers for degenerative lumbar spine diseases. CLINICAL RELEVANCE STATEMENT: The deep learning (DL)-based reconstruction algorithm may be used to further accelerate spine MRI imaging to reduce patient discomfort and increase the cost efficiency of spine MRI imaging. KEY POINTS: • By using deep learning (DL)-based reconstruction algorithm in combination with the accelerated MRI protocol, the average acquisition time was reduced by 32.3% as compared with the standard protocol. • DL-reconstructed images had similar or better quantitative/qualitative overall image quality and similar or better image quality for the delineation of most individual anatomical structures. • The average radiologist's sensitivity and specificity for the detection of major degenerative lumbar spine diseases, including central canal stenosis, neural foraminal stenosis, and disc herniation, on standard and DL-reconstructed images, were similar.

Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging for Language Mapping in Brain Tumor Surgery: Validation With Direct Cortical Stimulation and Cortico-Cortical Evoked Potential.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging-derived tractography (DTI-t) contribute to the localization of language areas, but their accuracy remains controversial. This study aimed to investigate the diagnostic performance of preoperative fMRI and DTI-t obtained with a simultaneous multi-slice technique using intraoperative direct cortical stimulation (DCS) or corticocortical evoked potential (CCEP) as reference standards. MATERIALS AND METHODS: This prospective study included 26 patients (23-74 years; male:female, 13:13) with tumors in the vicinity of Broca's area who underwent preoperative fMRI and DTI-t. A site-by-site comparison between preoperative (fMRI and DTI-t) and intraoperative language mapping (DCS or CCEP) was performed for 226 cortical sites to calculate the sensitivity and specificity of fMRI and DTI-t for mapping Broca's areas. For sites with positive signals on fMRI or DTI-t, the true-positive rate (TPR) was calculated based on the concordance and discordance between fMRI and DTI-t. RESULTS: Among 226 cortical sites, DCS was performed in 100 sites and CCEP was performed in 166 sites. The specificities of fMRI and DTI-t ranged from 72.4% (63/87) to 96.8% (122/126), respectively. The sensitivities of fMRI (except for verb generation) and DTI-t were 69.2% (9/13) to 92.3% (12/13) with DCS as the reference standard, and 40.0% (16/40) or lower with CCEP as the reference standard. For sites with preoperative fMRI or DTI-t positivity (n = 82), the TPR was high when fMRI and DTI-t were concordant (81.2% and 100% using DCS and CCEP, respectively, as the reference standards) and low when fMRI and DTI-t were discordant (≤ 24.2%). CONCLUSION: fMRI and DTI-t are sensitive and specific for mapping Broca's area compared with DCS and specific but insensitive compared with CCEP. A site with a positive signal on both fMRI and DTI-t represents a high probability of being an essential language area.

Body mass index and two-year change of in vivo Alzheimer's disease pathologies in cognitively normal older adults.

BACKGROUND: Low body mass index (BMI) or underweight status in late life is associated with an increased risk of dementia or Alzheimer's disease (AD). However, the relationship between late-life BMI and prospective longitudinal changes of in-vivo AD pathology has not been investigated. METHODS: This prospective longitudinal study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE). A total of 194 cognitive normal older adults were included in the analysis. BMI at baseline was measured, and two-year changes in brain Aß and tau deposition on PET imaging were used as the main outcomes. Linear mixed-effects (LME) models were used to examine the relationships between late-life BMI and longitudinal change in AD neuropathological biomarkers. RESULTS: A lower BMI at baseline was significantly associated with a greater increase in tau deposition in AD-signature region over 2 years (ß, -0.018; 95% CI, -0.028 to -0.004; p = .008), In contrast, BMI was not related to two-year changes in global Aß deposition (ß, 0.0002; 95% CI, -0.003 to 0.002, p = .671). An additional exploratory analysis for each sex showed lower baseline BMI was associated with greater increases in tau deposition in males (ß, -0.027; 95% CI, -0.046 to -0.009; p = 0.007), but not in females. DISCUSSION: The findings suggest that lower BMI in late-life may predict or contribute to the progression of tau pathology over the subsequent years in cognitively unimpaired older adults.

Serum Adiponectin and In Vivo Brain Amyloid Deposition in Cognitively Normal Older Adults: A Cohort Study.

High blood adiponectin has been associated with Alzheimer's disease (AD) dementia and related cognitive decline. We aimed to investigate the association between serum adiponectin level and in vivo AD pathologies. Cross-sectional and longitudinal study designs for the data of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease, an ongoing prospective cohort study that began in 2014. A total of 283 cognitively normal older adults between 55 and 90 years of age were included in community and memory clinic setting. Participants underwent comprehensive clinical assessments, measurement of serum adiponectin level, and multimodal brain imaging, including Pittsburgh compound-B positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and MRI at baseline and 2-year follow-up. Serum adiponectin level was positively associated with global beta-amyloid protein (Aß) retention and change therein over 2 years, but not with other AD neuroimaging markers including tau deposition, AD-related neurodegeneration, and white matter hyperintensities. Blood adiponectin level is associated with increased brain amyloid deposition, which suggests that adiponectin may be a potential target for therapeutic and preventive strategies against AD.

White matter integrity is associated with cognition and amyloid burden in older adult Koreans along the Alzheimer's disease continuum.

BACKGROUND: White matter (WM) microstructural changes in the hippocampal cingulum bundle (CBH) in Alzheimer's disease (AD) have been described in cohorts of largely European ancestry but are lacking in other populations. METHODS: We assessed the relationship between CBH WM integrity and cognition or amyloid burden in 505 Korean older adults aged ≥55 years, including 276 cognitively normal older adults (CN), 142 mild cognitive impairment (MCI), and 87 AD, recruited as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) at Seoul National University. RESULTS: Compared to CN, AD and MCI subjects showed decreased WM integrity in the bilateral CBH. Cognition, mood, and higher amyloid burden were also associated with poorer WM integrity in the CBH. CONCLUSION: These findings are consistent with patterns of WM microstructural damage previously reported in non-Hispanic White (NHW) MCI/AD cohorts, reinforcing existing evidence from predominantly NHW cohort studies.

Quantifying infarct core volume in ischemic stroke: What is the optimal threshold and parameters of computed tomography perfusion?

OBJECTIVE: Although computed tomography perfusion (CTP) is used to select and guide decision-making processes in patients with acute ischemic stroke, there is no clear standardization of the optimal threshold to predict ischemic core volume accurately. The infarct core volume with a relative cerebral blood flow(rCBF) threshold of < 30% is commonly used. We aimed to assess the volumetric agreement of the infarct core volume with different CTP parameters and thresholds using CTP software (RAPID, VITREA) and the infarct volume on diffusion-weighted imaging (DWI), with a short interval time (within 60 min) between CTP and follow-up DWI. MATERIALS AND METHODS: This retrospective study included 42 acute ischemic stroke patients with occlusion of the large artery in the anterior circulation between April 2017-November 2020. RAPID identified infarct core as tissue rCBF < 20-38%. VITREA defined the infarct core as cerebral blood volume (CBV) < 26-56%. Olea Sphere was used to measure infarct core volume on DWI. The CTP-infarct core volume with different thresholds of perfusion parameters (CBF threshold vs CBV threshold) were compared with DWI-infarct core volumes. RESULTS: The median time between CTP and DWI was 37.5min. The commonly used threshold of CBV< 41% (4.3 mL) resulted in lower median infarct core volume difference compared to the commonly used thresholds of rCBF < 30% (8.2mL). On the other hand, the optimal thresholds of CBV < 26% (-1.0mL; 95% CI, -53.9 to 58.1 mL; 0.945) resulted in the lowest median infarct core volume difference, narrowest limits of agreement, and largest interclass correlation coefficient compared with the optimal thresholds of rCBF < 38% (4.9 mL; 95% CI, -36.4 to 62.9 mL; 0.939). CONCLUSION: Our study found that the both optimal and commonly used thresholds of CBV provided a more accurate prediction of the infarct core volume in patients with AIS than rCBF.

Risk of thyroid cancer in a lung cancer screening population of the National Lung Screening Trial according to the presence of incidental thyroid nodules detected on low-dose chest CT.

PURPOSE: This study evaluated thyroid cancer risk in a lung cancer screening population according to the presence of an incidental thyroid nodule (ITN) detected on low-dose chest computed tomography (LDCT). METHODS: Of 47,837 subjects who underwent LDCT, a lung cancer screening population according to the National Lung Screening Trial results was retrospectively enrolled. The prevalence of ITN on LDCT was calculated, and the ultrasonography (US)/fine-needle aspiration (FNA)-based risk of thyroid cancer according to the presence of ITN on LDCT was compared using the Fisher exact or Student t-test as appropriate. RESULTS: Of the 2,329 subjects (female:male=44:2,285; mean age, 60.9±4.9 years), the prevalence of ITN on LDCT was 4.8% (111/2,329). The incidence of thyroid cancer was 0.8% (18/2,329, papillary thyroid microcarcinomas [PTMCs]) and was higher in the ITN-positive group than in the ITN-negative group (3.6% [4/111] vs. 0.6% [14/2,218], P=0.009). Among the 2,011 subjects who underwent both LDCT and thyroid US, all risks were higher (P<0.001) in the ITNpositive group than in the ITN-negative group: presence of thyroid nodule on US, 94.1% (95/101) vs. 48.6% (928/1,910); recommendation of FNA according to the American Thyroid Association guideline and Korean Thyroid Imaging Reporting and Data System guideline, 41.2% (42/101) vs. 2.4% (46/1,910) and 39.6% (40/101) vs. 1.9% (37/1,910), respectively. CONCLUSION: Despite a higher risk of thyroid cancer in the LDCT ITN-positive group than in the ITN-negative group in a lung cancer screening population, all cancers were PTMCs. A heavy smoking history may not necessitate thorough screening US for thyroid incidentalomas.

Low Ankle-Brachial Index Relates to Alzheimer-Signature Cerebral Glucose Metabolism in Cognitively Impaired Older Adults.

BACKGROUND: Ankle-brachial index (ABI), an indicator of atherosclerosis or arterial stiffness, has been associated with Alzheimer's disease (AD) dementia and related cognitive impairment. Nevertheless, only limited information is available regarding its contribution to brain alterations leading to cognitive decline in late-life. OBJECTIVE: We aimed to investigate the relationship of ABI with in vivo AD pathologies and cerebrovascular injury in cognitively impaired older adults. METHODS: Total 127 cognitively impaired (70 mild cognitive impairment and 57 AD dementia) individuals, who participated in an ongoing prospective cohort study, were included. All participants underwent comprehensive clinical and neuropsychological assessment, ABI measurement, apolipoprotein E (APOE) ɛ4 genotyping, and multi-modal brain imaging including [11C] Pittsburgh Compound B (PiB)-positron emission tomography (PET) and [18F] fludeoxyglucose (FDG)-PET, and MRI. RESULTS: General linear model analysis showed significant relationship between ABI strata (low ABI: <1.00, normal ABI: 1.00-1.29, and high ABI: ≥1.30) and AD-signature region cerebral glucose metabolism (AD-CM), even after controlling age, sex, clinical dementia rating-sum of box, and APOE ɛ4 positivity (p = 0.029). Post hoc comparison revealed that low ABI had significantly lower AD-CM than middle and high ABI, while no difference of AD-CM was found between middle and high ABI. There was no significant difference of global Aß deposition, AD-signature region cortical thickness, and white matter hyperintensity volume between the three ABI strata. CONCLUSION: Our findings suggest that lower ABI, likely related to atherosclerosis, may contribute to the aggravation of AD-related regional neurodegeneration in cognitively impaired older adults.

Circadian rest-activity rhythm and longitudinal brain changes underlying late-life cognitive decline.

AIM: The neurobiological substrates underlying the relationship of circadian rest-activity rhythm (RAR) alteration with accelerated late-life cognitive decline are not clearly understood. In the present study, the longitudinal relationship of objectively measured circadian RAR with in vivo Alzheimer disease (AD) pathologies and cerebrovascular injury was investigated in older adults without dementia. METHODS: The present study included 129 participants without dementia who participated in the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease) cohort. All participants underwent actigraphy at baseline and two consecutive [11 C] Pittsburgh compound-B positron emission tomography (PET), [18 F] fluorodeoxyglucose-PET, magnetic resonance imaging, and Mini-Mental State Examination (MMSE) at baseline and at a 2-year follow-up assessment. The associations of circadian RAR with annualized change in neuroimaging measures including global amyloid-beta retention, AD-signature region cerebral glucose metabolism (AD-CM), and white matter hyperintensity volume were examined. RESULTS: Delayed acrophase at baseline was significantly associated with greater annualized decline of AD-CM over a 2-year period, but not with that of other neuroimaging measures. In contrast, other circadian RAR parameters at baseline had no association with annualized change of any neuroimaging measures. Annualized decline of AD-CM was also significantly positively associated with the annual change in MMSE scores. Furthermore, a mediation analysis showed that greater reduction in AD-CM mediated the effect of delayed acrophase at baseline on faster decline of MMSE score. CONCLUSION: The findings indicate that delayed acrophase in late life may cause or predict hypometabolism at AD-signature brain regions, which underlies cognitive decline in the near future.

Enlarged perivascular spaces are associated with decreased brain tau deposition.

AIMS: The aim of this study was to investigate the associations of enlarged perivascular spaces (EPVS) in the basal ganglia (BG) and centrum semiovale (CSO) with beta-amyloid (Aß) and tau deposition in older adults with a diverse cognitive spectrum. METHODS: A total of 163 (68 cognitively normal and 95 cognitively impaired) older participants underwent [11 C] Pittsburgh compound B and [18 F] AV-1451 PET, and MRI. EPVS in the BG and CSO and other small vessel disease markers, such as white matter hyperintensities, lacunes, and deep and lobar microbleeds, were assessed. RESULTS: Increased EPVS in the BG showed a significant association with lower cerebral tau deposition, even after controlling for other small vessel disease markers. Further exploratory analyses showed that this association was significant in cognitively impaired, Aß-positive, or APOE4-positive individuals, but not significant in the cognitively normal, Aß-negative, or APOE4-negative participants. In contrast to EPVS in the BG, EPVS in the CSO did not have any relationship with cerebral tau deposition. In addition, none of the two types of EPVS were associated with cerebral Aß deposition. CONCLUSION: Brain tau deposition appears to be reduced with increased EPVS in the BG, especially in individuals with cognitive impairment, pathological amyloid burden, or genetic Alzheimer's disease risk.

Detection of Cerebral Microbleeds in MR Images Using a Single-Stage Triplanar Ensemble Detection Network (TPE-Det).

BACKGROUND: Cerebral microbleeds (CMBs) are microscopic brain hemorrhages with implications for various diseases. Automated detection of CMBs is a challenging task due to their wide distribution throughout the brain, small size, and visual similarity to their mimics. For this reason, most of the previously proposed methods have been accomplished through two distinct stages, which may lead to difficulties in integrating them into clinical workflows. PURPOSE: To develop a clinically feasible end-to-end CMBs detection network with a single-stage structure utilizing 3D information. This study proposes triplanar ensemble detection network (TPE-Det), ensembling 2D convolutional neural networks (CNNs) based detection networks on axial, sagittal, and coronal planes. STUDY TYPE: Retrospective. SUBJECTS: Two datasets (DS1 and DS2) were used: 1) 116 patients with 367 CMBs and 12 patients without CMBs for training, validation, and testing (70.39 ± 9.30 years, 68 women, 60 men, DS1); 2) 58 subjects with 148 microbleeds and 21 subjects without CMBs only for testing (76.13 ± 7.89 years, 47 women, 32 men, DS2). FIELD STRENGTH/SEQUENCE: A 3 T field strength and 3D GRE sequence scan for SWI reconstructions. ASSESSMENT: The sensitivity, FPavg (false-positive per subject), and precision measures were computed and analyzed with statistical analysis. STATISTICAL TESTS: A paired t-test was performed to investigate the improvement of detection performance by the suggested ensembling technique in this study. A P value < 0.05 was considered significant. RESULTS: The proposed TPE-Det detected CMBs on the DS1 testing set with a sensitivity of 96.05% and an FPavg of 0.88, presenting statistically significant improvement. Even when the testing on DS2 was performed without retraining, the proposed model provided a sensitivity of 85.03% and an FPavg of 0.55. The precision was significantly higher than the other models. DATA CONCLUSION: The ensembling of multidimensional networks significantly improves precision, suggesting that this new approach could increase the benefits of detecting lesions in the clinic. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.