Comparative Performance of Susceptibility Map-Weighted MRI According to the Acquisition Planes in the Diagnosis of Neurodegenerative Parkinsonism.

OBJECTIVE: To evaluate the diagnostic performance of susceptibility map-weighted imaging (SMwI) taken in different acquisition planes for discriminating patients with neurodegenerative parkinsonism from those without. MATERIALS AND METHODS: This retrospective, observational, single-institution study enrolled consecutive patients who visited movement disorder clinics and underwent brain MRI and 18F-FP-CIT PET between September 2021 and December 2021. SMwI images were acquired in both the oblique (perpendicular to the midbrain) and the anterior commissure-posterior commissure (AC-PC) planes. Hyperintensity in the substantia nigra was determined by two neuroradiologists. 18F-FP-CIT PET was used as the reference standard. Inter-rater agreement was assessed using Cohen's kappa coefficient. The diagnostic performance of SMwI in the two planes was analyzed separately for the right and left substantia nigra. Multivariable logistic regression analysis with generalized estimating equations was applied to compare the diagnostic performance of the two planes. RESULTS: In total, 194 patients were included, of whom 105 and 103 had positive results on 18F-FP-CIT PET in the left and right substantia nigra, respectively. Good inter-rater agreement in the oblique (κ = 0.772/0.658 for left/right) and AC-PC planes (0.730/0.741 for left/right) was confirmed. The pooled sensitivities for two readers were 86.4% (178/206, left) and 83.3% (175/210, right) in the oblique plane and 87.4% (180/206, left) and 87.6% (184/210, right) in the AC-PC plane. The pooled specificities for two readers were 83.5% (152/182, left) and 82.0% (146/178, right) in the oblique plane, and 83.5% (152/182, left) and 86.0% (153/178, right) in the AC-PC plane. There were no significant differences in the diagnostic performance between the two planes (P > 0.05). CONCLUSION: There are no significant difference in the diagnostic performance of SMwI performed in the oblique and AC-PC plane in discriminating patients with parkinsonism from those without. This finding affirms that each institution may choose the imaging plane for SMwI according to their clinical settings.

Mapping Changes in Glutamate with Glutamate-Weighted MRI in Forced Swim Test Model of Depression in Rats.

Chemical exchange saturation transfer with glutamate (GluCEST) imaging is a novel technique for the non-invasive detection and quantification of cerebral Glu levels in neuromolecular processes. Here we used GluCEST imaging and 1H magnetic resonance spectroscopy (1H MRS) to assess in vivo changes in Glu signals within the hippocampus in a rat model of depression induced by a forced swim test. The forced swimming test (FST) group exhibited markedly reduced GluCEST-weighted levels and Glu concentrations when examined using 1H MRS in the hippocampal region compared to the control group (GluCEST-weighted levels: 3.67 ± 0.81% vs. 5.02 ± 0.44%, p < 0.001; and Glu concentrations: 6.560 ± 0.292 µmol/g vs. 7.133 ± 0.397 µmol/g, p = 0.001). Our results indicate that GluCEST imaging is a distinctive approach to detecting and monitoring Glu levels in a rat model of depression. Furthermore, the application of GluCEST imaging may provide a deeper insight into the neurochemical involvement of glutamate in various psychiatric disorders.

Development of statistical auto-segmentation method for diffusion restriction gray matter lesions in patients with newly diagnosed sporadic Creutzfeldt-Jakob disease.

Quantification of diffusion restriction lesions in sporadic Creutzfeldt-Jakob disease (sCJD) may provide information of the disease burden. We aim to develop an automatic segmentation model for sCJD and to evaluate the volume of disease extent as a prognostic marker for overall survival. Fifty-six patients (mean age ± SD, 61.2 ± 9.9 years) were included from February 2000 to July 2020. A threshold-based segmentation was used to obtain abnormal signal intensity masks. Segmented volumes were compared with the visual grade. The Dice similarity coefficient was calculated to measure the similarity between the automatic vs. manual segmentation. Cox proportional hazards regression analysis was performed to evaluate the volume of disease extent as a prognostic marker. The automatic segmentation showed good correlation with the visual grading. The cortical lesion volumes significantly increased as the visual grade aggravated (extensive: 112.9 ± 73.2; moderate: 45.4 ± 30.4; minimal involvement: 29.6 ± 18.1 mm3) (P < 0.001). The deep gray matter lesion volumes were significantly higher for positive than for negative involvement of the deep gray matter (5.6 ± 4.6 mm3 vs. 1.0 ± 1.3 mm3, P < 0.001). The mean Dice similarity coefficients were 0.90 and 0.94 for cortical and deep gray matter lesions, respectively. However, the volume of disease extent was not associated with worse overall survival (cortical extent: P = 0.07; deep gray matter extent: P = 0.12).

Corrigendum: Development and validation of a deep learning-based automatic segmentation model for assessing intracranial volume: comparison with NeuroQuant, FreeSurfer, and SynthSeg.

[This corrects the article DOI: 10.3389/fneur.2023.1221892.].

Detection rate of brain MR and MR angiography for neuroimaging abnormality in patients with newly diagnosed left-sided infective endocarditis.

We aimed to investigate the detection rate of brain MR and MR angiography for neuroimaging abnormality in newly diagnosed left-sided infective endocarditis patients with/without neurological symptoms. This retrospective study included consecutive patients with definite or possible left-sided infective endocarditis according to the modified Duke criteria who underwent brain MRI and MR angiography between March 2015 and October 2020. The detection rate for neuroimaging abnormality on MRI was defined as the number of patients with positive brain MRI findings divided by the number of patients with left-sided infective endocarditis. Positive imaging findings included acute ischemic lesions, cerebral microbleeds, hemorrhagic lesions, and infectious aneurysms. In addition, aneurysm rupture rate and median period to aneurysm rupture were evaluated on follow-up studies. A total 115 patients (mean age: 55 years ± 19; 65 men) were included. The detection rate for neuroimaging abnormality was 77% (89/115). The detection rate in patients without neurological symptoms was 70% (56/80). Acute ischemic lesions, cerebral microbleeds, and hemorrhagic lesions including superficial siderosis and intracranial hemorrhage were detected on MRI in 56% (64/115), 57% (66/115), and 20% (23/115) of patients, respectively. In particular, infectious aneurysms were detected on MR angiography in 3% of patients (4/115), but MR angiography in 5 patients (4.3%) was insignificant for infectious aneurysm, which were detected using CT angiography (n = 3) and digital subtraction angiography (n = 2) during follow-up. Among the 9 infectious aneurysm patients, aneurysm rupture occurred in 4 (44%), with a median period of aneurysm rupture of 5 days. The detection rate of brain MRI for neuroimaging abnormality in newly diagnosed left-sided infective endocarditis patients was high (77%), even without neurological symptoms (70%).

Amphiregulin normalizes altered circuit connectivity for social dominance of the CRTC3 knockout mouse.

Social hierarchy has a profound impact on social behavior, reward processing, and mental health. Moreover, lower social rank can lead to chronic stress and often more serious problems such as bullying victims of abuse, suicide, or attack to society. However, its underlying mechanisms, particularly their association with glial factors, are largely unknown. In this study, we report that astrocyte-derived amphiregulin plays a critical role in the determination of hierarchical ranks. We found that astrocytes-secreted amphiregulin is directly regulated by cAMP response element-binding (CREB)-regulated transcription coactivator 3 (CRTC3) and CREB. Mice with systemic and astrocyte-specific CRTC3 deficiency exhibited a lower social rank with reduced functional connectivity between the prefrontal cortex, a major social hierarchy center, and the parietal cortex. However, this effect was reversed by astrocyte-specific induction of amphiregulin expression, and the epidermal growth factor domain was critical for this action of amphiregulin. These results provide evidence of the involvement of novel glial factors in the regulation of social dominance and may shed light on the clinical application of amphiregulin in the treatment of various psychiatric disorders.

Development and validation of a deep learning-based automatic segmentation model for assessing intracranial volume: comparison with NeuroQuant, FreeSurfer, and SynthSeg.

Background and purpose: To develop and validate a deep learning-based automatic segmentation model for assessing intracranial volume (ICV) and to compare the accuracy determined by NeuroQuant (NQ), FreeSurfer (FS), and SynthSeg. Materials and methods: This retrospective study included 60 subjects [30 Alzheimer's disease (AD), 21 mild cognitive impairment (MCI), 9 cognitively normal (CN)] from a single tertiary hospital for the training and validation group (50:10). The test group included 40 subjects (20 AD, 10 MCI, 10 CN) from the ADNI dataset. We propose a robust ICV segmentation model based on the foundational 2D UNet architecture trained with four types of input images (both single and multimodality using scaled or unscaled T1-weighted and T2-FLAIR MR images). To compare with our model, NQ, FS, and SynthSeg were also utilized in the test group. We evaluated the model performance by measuring the Dice similarity coefficient (DSC) and average volume difference. Results: The single-modality model trained with scaled T1-weighted images showed excellent performance with a DSC of 0.989 ± 0.002 and an average volume difference of 0.46% ± 0.38%. Our multimodality model trained with both unscaled T1-weighted and T2-FLAIR images showed similar performance with a DSC of 0.988 ± 0.002 and an average volume difference of 0.47% ± 0.35%. The overall average volume difference with our model showed relatively higher accuracy than NQ (2.15% ± 1.72%), FS (3.69% ± 2.93%), and SynthSeg (1.88% ± 1.18%). Furthermore, our model outperformed the three others in each subgroup of patients with AD, MCI, and CN subjects. Conclusion: Our deep learning-based automatic ICV segmentation model showed excellent performance for the automatic evaluation of ICV.

Cerebral Glutamate Alterations Using Chemical Exchange Saturation Transfer Imaging in a Rat Model of Lipopolysaccharide-Induced Sepsis.

Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool to detect glutamate signal alterations caused by neuroinflammation. This study aimed to visualize and quantitatively evaluate hippocampal glutamate alterations in a rat model of sepsis-induced brain injury using GluCEST and proton magnetic resonance spectroscopy (1H-MRS). Twenty-one Sprague Dawley rats were divided into three groups (sepsis-induced groups (SEP05, n = 7 and SEP10, n = 7) and controls (n = 7)). Sepsis was induced through a single intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 5 mg/kg (SEP05) or 10 mg/kg (SEP10). GluCEST values and 1H-MRS concentrations in the hippocampal region were quantified using conventional magnetization transfer ratio asymmetry and a water scaling method, respectively. In addition, we examined immunohistochemical and immunofluorescence staining to observe the immune response and activity in the hippocampal region after LPS exposure. The GluCEST and 1H-MRS results showed that GluCEST values and glutamate concentrations were significantly higher in sepsis-induced rats than those in controls as the LPS dose increased. GluCEST imaging may be a helpful technique for defining biomarkers to estimate glutamate-related metabolism in sepsis-associated diseases.

Development and validation of an automatic classification algorithm for the diagnosis of Alzheimer's disease using a high-performance interpretable deep learning network.

OBJECTIVES: To develop and validate an automatic classification algorithm for diagnosing Alzheimer's disease (AD) or mild cognitive impairment (MCI). METHODS AND MATERIALS: This study evaluated a high-performance interpretable network algorithm (TabNet) and compared its performance with that of XGBoost, a widely used classifier. Brain segmentation was performed using a commercially approved software. TabNet and XGBoost were trained on the volumes or radiomics features of 102 segmented regions for classifying subjects into AD, MCI, or cognitively normal (CN) groups. The diagnostic performances of the two algorithms were compared using areas under the curves (AUCs). Additionally, 20 deep learning-based AD signature areas were investigated. RESULTS: Between December 2014 and March 2017, 161 AD, 153 MCI, and 306 CN cases were enrolled. Another 120 AD, 90 MCI, and 141 CN cases were included for the internal validation. Public datasets were used for external validation. TabNet with volume features had an AUC of 0.951 (95% confidence interval [CI], 0.947-0.955) for AD vs CN, which was similar to that of XGBoost (0.953 [95% CI, 0.951-0.955], p = 0.41). External validation revealed the similar performances of two classifiers using volume features (0.871 vs. 0.871, p = 0.86). Likewise, two algorithms showed similar performances with one another in classifying MCI. The addition of radiomics data did not improve the performance of TabNet. TabNet and XGBoost focused on the same 13/20 regions of interest, including the hippocampus, inferior lateral ventricle, and entorhinal cortex. CONCLUSIONS: TabNet shows high performance in AD classification and detailed interpretation of the selected regions. CLINICAL RELEVANCE STATEMENT: Using a high-performance interpretable deep learning network, the automatic classification algorithm assisted in accurate Alzheimer's disease detection using 3D T1-weighted brain MRI and detailed interpretation of the selected regions. KEY POINTS: • MR volumetry data revealed that TabNet had a high diagnostic performance in differentiating Alzheimer's disease (AD) from cognitive normal cases, which was comparable with that of XGBoost. • The addition of radiomics data to the volume data did not improve the diagnostic performance of TabNet. • Both TabNet and XGBoost selected the clinically meaningful regions of interest in AD, including the hippocampus, inferior lateral ventricle, and entorhinal cortex.

Is aryl hydrocarbon receptor antagonism after ischemia effective in alleviating acute hepatic ischemia-reperfusion injury in rats?

Aryl hydrocarbon receptors (AhRs) have been reported to be important mediators of ischemic injury in the brain. Furthermore, the pharmacological inhibition of AhR activation after ischemia has been shown to attenuate cerebral ischemia-reperfusion (IR) injury. Here, we investigated whether AhR antagonist administration after ischemia was also effective in ameliorating hepatic IR injury. A 70% partial hepatic IR (45-min ischemia and 24-h reperfusion) injury was induced in rats. We administered 6,2',4'-trimethoxyflavone (TMF, 5 mg/kg) intraperitoneally 10 min after ischemia. Hepatic IR injury was observed using serum, magnetic resonance imaging-based liver function indices, and liver samples. TMF-treated rats showed significantly lower relative enhancement (RE) values and serum alanine aminotransferase (ALT) and aspartate aminotransferase levels than did untreated rats at 3 h after reperfusion. After 24 h of reperfusion, TMF-treated rats had significantly lower RE values, ΔT1 values, serum ALT levels, and necrotic area percentage than did untreated rats. The expression of the apoptosis-related proteins, Bax and cleaved caspase-3, was significantly lower in TMF-treated rats than in untreated rats. This study demonstrated that inhibition of AhR activation after ischemia was effective in ameliorating IR-induced liver injury in rats.

Risk estimation for idiopathic normal-pressure hydrocephalus: development and validation of a brain morphometry-based nomogram.

OBJECTIVES: To develop and validate a nomogram based on MRI features for predicting iNPH. METHODS: Patients aged ≥ 60 years (clinically diagnosed with iNPH, Parkinson's disease, or Alzheimer's disease or healthy controls) who underwent MRI including three-dimensional T1-weighted volumetric MRI were retrospectively identified from two tertiary referral hospitals (one hospital for derivation set and the other for validation set). Clinical and imaging features for iNPH were assessed. Deep learning-based brain segmentation software was used for 3D volumetry. A prediction model was developed using logistic regression and transformed into a nomogram. The performance of the nomogram was assessed with respect to discrimination and calibration abilities. The nomogram was internally and externally validated. RESULTS: A total of 452 patients (mean age ± SD, 73.2 ± 6.5 years; 200 men) were evaluated as the derivation set. One hundred eleven and 341 patients were categorized into the iNPH and non-iNPH groups, respectively. In multivariable analysis, high-convexity tightness (odds ratio [OR], 35.1; 95% CI: 4.5, 275.5), callosal angle < 90° (OR, 12.5; 95% CI: 3.1, 50.0), and normalized lateral ventricle volume (OR, 4.2; 95% CI: 2.7, 6.7) were associated with iNPH. The nomogram combining these three variables showed an area under the curve of 0.995 (95% CI: 0.991, 0.999) in the study sample, 0.994 (95% CI: 0.990, 0.998) in the internal validation sample, and 0.969 (95% CI: 0.940, 0.997) in the external validation sample. CONCLUSION: A brain morphometry-based nomogram including high-convexity tightness, callosal angle < 90°, and normalized lateral ventricle volume can help accurately estimate the probability of iNPH. KEY POINTS: • The nomogram with MRI findings (high-convexity tightness, callosal angle, and normalized lateral ventricle volume) helped in predicting the probability of idiopathic normal-pressure hydrocephalus. • The nomogram may facilitate the prediction of idiopathic normal-pressure hydrocephalus and consequently avoid unnecessary invasive procedures such as the cerebrospinal fluid tap test, drainage test, and cerebrospinal fluid shunt surgery.

Preclinical Long-term Magnetic Resonance Imaging Study of Silymarin Liver-protective Effects.

Background and Aims: Efficacy evaluations with preclinical magnetic resonance imaging (MRI) are uncommon, but MRI in the preclinical phase of drug development provides information that is useful for longitudinal monitoring. The study aim was to monitor the protective effectiveness of silymarin with multiparameter MRI and biomarkers in a thioacetamide (TAA)-induced model of liver injury in rats. Correlation analysis was conducted to assess compare the monitoring of liver function by MRI and biomarkers. Methods: TAA was injected three times a week for 8 weeks to generate a disease model (TAA group). In the TAA and silymarin-treated (TAA-SY) groups, silymarin was administered three times weekly from week 4. MR images were acquired at 0, 2, 4, 6, and 8 weeks in the control, TAA, and TAA-SY groups. Results: The area under the curve to maximum time (AUCtmax) and T2* values of the TAA group decreased over the study period, but the serological markers of liver abnormality increased significantly more than those in the control group. In the TAA-SY group, MRI and serological biomarkers indicated attenuation of liver function as in the TAA group. However, pattern changes were observed from week 6 to comparable levels in the control group with silymarin treatment. Negative correlations between either AUCtmax or T2* values and the serological biomarkers were observed. Conclusions: Silymarin had hepatoprotective effects on TAA-induced liver injury and demonstrated the usefulness of multiparametric MRI to evaluate efficacy in preclinical studies of liver drug development.

[Brain MRI-Based Artificial Intelligence Software in Patients with Neurodegenerative Diseases: Current Status]. / 퇴행성 뇌질환에서 뇌 ìžê¸°ê³µëª ì˜ìƒ 기반 인공지능 소프트웨어 활용의 현재.

The incidence of neurodegenerative diseases in the older population has increased in recent years. A considerable number of studies have been performed to characterize these diseases. Imaging analysis is an important biomarker for the diagnosis of neurodegenerative disease. Objective and reliable assessment and precise detection are important for the early diagnosis of neurodegenerative diseases. Artificial intelligence (AI) using brain MRI applied to the study of neurodegenerative diseases could promote early diagnosis and optimal decisions for treatment plans. MRI-based AI software have been developed and studied worldwide. Representatively, there are MRI-based volumetry and segmentation software. In this review, we present the development process of brain volumetry analysis software in neurodegenerative diseases, currently used and developed AI software for neurodegenerative disease in the Republic of Korea, probable uses of AI in the future, and AI software limitations.

Diagnostic performance of deep learning-based automatic white matter hyperintensity segmentation for classification of the Fazekas scale and differentiation of subcortical vascular dementia.

PURPOSE: To validate the diagnostic performance of commercially available, deep learning-based automatic white matter hyperintensity (WMH) segmentation algorithm for classifying the grades of the Fazekas scale and differentiating subcortical vascular dementia. METHODS: This retrospective, observational, single-institution study investigated the diagnostic performance of a deep learning-based automatic WMH volume segmentation to classify the grades of the Fazekas scale and differentiate subcortical vascular dementia. The VUNO Med-DeepBrain was used for the WMH segmentation system. The system for segmentation of WMH was designed with convolutional neural networks, in which the input image was comprised of a pre-processed axial FLAIR image, and the output was a segmented WMH mask and its volume. Patients presented with memory complaint between March 2017 and June 2018 were included and were split into training (March 2017-March 2018, n = 596) and internal validation test set (April 2018-June 2018, n = 204). RESULTS: Optimal cut-off values to categorize WMH volume as normal vs. mild/moderate/severe, normal/mild vs. moderate/severe, and normal/mild/moderate vs. severe were 3.4 mL, 9.6 mL, and 17.1 mL, respectively, and the AUC were 0.921, 0.956 and 0.960, respectively. When differentiating normal/mild vs. moderate/severe using WMH volume in the test set, sensitivity, specificity, and accuracy were 96.4%, 89.9%, and 91.7%, respectively. For distinguishing subcortical vascular dementia from others using WMH volume, sensitivity, specificity, and accuracy were 83.3%, 84.3%, and 84.3%, respectively. CONCLUSION: Deep learning-based automatic WMH segmentation may be an accurate and promising method for classifying the grades of the Fazekas scale and differentiating subcortical vascular dementia.

Diagnostic yield of TOF-MRA for detecting incidental vascular lesions in patients with cognitive impairment: An observational cohort study.

Objectives: The role of three-dimensional (3D) TOF-MRA in patients with cognitive impairment is not well established. We evaluated the diagnostic yield of 3D TOF-MRA for detecting incidental extra- or intracranial artery stenosis and intracranial aneurysm in this patient group. Methods: This retrospective study included patients with cognitive impairment undergoing our brain MRI protocol from January 2013 to February 2020. The diagnostic yield of TOF-MRA for detecting incidental vascular lesions was calculated. Patients with positive TOF-MRA results were reviewed to find whether additional treatment was performed. Logistic regression analysis was conducted to identify the clinical risk factors for positive TOF-MRA findings. Results: In total, 1,753 patients (mean age, 70.2 ± 10.6 years; 1,044 women) were included; 199 intracranial aneurysms were detected among 162 patients (9.2%, 162/1,753). A 3D TOF-MRA revealed significant artery stenoses (>50% stenosis) in 162 patients (9.2%, 162/1,753). The overall diagnostic yield of TOF-MRA was 16.8% (294/1,753). Among them, 92 patients (31.3%, 92/294) underwent either medical therapy, endovascular intervention, or surgery. In total, eighty-one patients with stenosis were prescribed with either antiplatelet medications or lipid-lowering agent. In total, fifteen patients (aneurysm: 11 patients, stenosis: 4 patients) were further treated with endovascular intervention or surgery. Thus, the "number needed to scan" was 19 for identifying one patient requiring treatment. Multivariate logistic regression analysis showed that being female (odds ratio [OR] 2.05) and old age (OR 1.04) were the independent risk factors for intracranial aneurysm; being male (OR 1.52), old age (OR 1.06), hypertension (OR 1.78), and ischemic heart disease history (OR 2.65) were the independent risk factors for significant artery stenosis. Conclusions: Our study demonstrated the potential benefit of 3D TOF-MRA, given that it showed high diagnostic yield for detecting vascular lesions in patients with cognitive impairment and the considerable number of these lesions required further treatment. A 3D TOF-MRA may be included in the routine MR protocol for the work-up of this patient population, especially in older patients and patients with vascular risk factors.

Diagnostic yield of MR myelography in patients with newly diagnosed spontaneous intracranial hypotension: a systematic review and meta-analysis.

OBJECTIVES: To investigate the pooled diagnostic yield of MR myelography in patients with newly diagnosed spontaneous intracranial hypotension (SIH). METHODS: A literature search of the MEDLINE/PubMed and Embase databases was conducted until July 25, 2021, including studies with the following inclusion criteria: (a) population: patients with newly diagnosed SIH; (b) diagnostic modality: MR myelography or MR myelography with intrathecal gadolinium for evaluation of CSF leakage; (c) outcomes: diagnostic yield of MR myelography or MR myelography with intrathecal gadolinium. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. DerSimonian-Laird random-effects modeling was used to calculate the pooled estimates. Subgroup analysis regarding epidural fluid collection and meta-regression were additionally performed. RESULTS: Fifteen studies with 643 patients were included. Eight studies used MR myelography with intrathecal gadolinium, and 11 used MR myelography. The overall quality of the included studies was moderate. The pooled diagnostic yield of MR myelography was 86% (95% CI, 80-91%) and that of MR myelography with intrathecal gadolinium was 83% (95% CI, 51-96%). There was no significant difference in pooled diagnostic yield between MR myelography and MR myelography with intrathecal gadolinium (p = 0.512). In subgroup analysis, the pooled diagnostic yield of the epidural fluid collection was 91% (95% CI, 84-94%). In meta-regression, the diagnostic yield was unaffected regardless of consecutive enrollment, magnet strength, or 2D/3D. CONCLUSIONS: MR myelography had a high diagnostic yield in patients with SIH. MR myelography is non-invasive and not inferior to MR myelography with intrathecal gadolinium. KEY POINTS: • The pooled diagnostic yield of MR myelography was 86% (95% CI, 80-91%) in patients with spontaneous intracranial hypotension. • There was no significant difference in pooled diagnostic yield between MR myelography and MR myelography with intrathecal gadolinium. • MR myelography is non-invasive and not inferior to MR myelography with intrathecal gadolinium.

Diagnostic performance of hippocampal volumetry in Alzheimer's disease or mild cognitive impairment: a meta-analysis.

OBJECTIVE: To evaluate the diagnostic performance of hippocampal volumetry for Alzheimer's disease (AD) or mild cognitive impairment (MCI). METHODS: The MEDLINE and Embase databases were searched for articles that evaluated the diagnostic performance of hippocampal volumetry in differentiating AD or MCI from normal controls, published up to March 6, 2022. The quality of the articles was evaluated by the QUADAS-2 tool. A bivariate random-effects model was used to pool sensitivity, specificity, and area under the curve. Sensitivity analysis and meta-regression were conducted to explain study heterogeneity. The diagnostic performance of entorhinal cortex volumetry was also pooled. RESULTS: Thirty-three articles (5157 patients) were included. The pooled sensitivity and specificity for AD were 82% (95% confidence interval [CI], 77-86%) and 87% (95% CI, 82-91%), whereas those for MCI were 60% (95% CI, 51-69%) and 75% (95% CI, 67-81%), respectively. No difference in the diagnostic performance was observed between automatic and manual segmentation (p = 0.11). MMSE scores, study design, and the reference standard being used were associated with study heterogeneity (p < 0.01). Subgroup analysis demonstrated a higher diagnostic performance of entorhinal cortex volumetry for both AD (pooled sensitivity: 88% vs. 79%, specificity: 92% vs. 89%, p = 0.07) and MCI (pooled sensitivity: 71% vs. 55%, specificity: 83% vs. 68%, p = 0.06). CONCLUSIONS: Our meta-analysis demonstrated good diagnostic performance of hippocampal volumetry for AD or MCI. Entorhinal cortex volumetry might have superior diagnostic performance to hippocampal volumetry. However, due to a small number of studies, the diagnostic performance of entorhinal cortex volumetry is yet to be determined. KEY POINTS: • The pooled sensitivity and specificity of hippocampal volumetry for Alzheimer's disease were 82% and 87%, whereas those for mild cognitive impairment were 60% and 75%, respectively. • No significant difference in the diagnostic performance was observed between automatic and manual segmentation. • Subgroup analysis demonstrated superior diagnostic performance of entorhinal cortex volumetry for AD (pooled sensitivity: 88%, specificity: 92%) and MCI (pooled sensitivity: 71%, specificity: 83%).

Amide Proton Transfer-weighted 7-T MRI Contrast of Myelination after Cuprizone Administration.

Background Investigations of amide proton signal changes in the white matter of demyelinating diseases may provide important biophysical information for diagnostic and prognostic assessments. Purpose To evaluate amide proton signals in cuprizone-induced rats using amide proton transfer-weighted (APTw) MRI, which provides in vivo image contrast by changing amide proton concentrations during demyelination (DEM) and subsequent remyelination (REM). Materials and Methods In this animal study, APTw 7-T MRI was performed in 21 male Wistar rats divided into cuprizone-induced (n = 14) and control (n = 7) groups from February to August 2020. The cuprizone-induced group was further subdivided into DEM (n = 7) and REM (n = 7) groups. Seven weeks after cuprizone feeding, rats in the DEM group were killed prior to transmission electron microscopy and myelin staining, while rats in the REM group were changed to a normal chow diet and fed for 5 weeks. In each group, the APTw signals were calculated using a conventional magnetization transfer ratio at 3.5 ppm based on regions of interest in the corpus callosum. Statistical differences in APTw signals among the groups were analyzed with one-way analysis of variance followed by Tukey post hoc tests. Results The mean APTw signals in the control and DEM groups were -4.42% ± 0.60 (standard deviation) (95% CI: -4.98, -3.86) and -2.57% ± 0.48 (95% CI: -3.01, -2.12), respectively, indicating higher in vivo APTw signals in the DEM lesion (P < .001). After REM, mean APTw signal in the REM group was -3.83% ± 0.67 (95% CI: -4.45, -3.22), similar to that in the control group (P = .18) and lower than that in the DEM group (P < .001). Conclusion Significant amide proton transfer-weighted (APTw) metric changes coupled with the histologic characteristics of the demyelination and remyelination processes indicate the potential usefulness of APTw 7-T MRI to monitor earlier myelination processes. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by van Zijl in this issue.

Temporal Changes in In Vivo Glutamate Signal during Demyelination and Remyelination in the Corpus Callosum: A Glutamate-Weighted Chemical Exchange Saturation Transfer Imaging Study.

BACKGROUND: Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool that can be used to detect changes in glutamate levels in vivo and could also be helpful in the diagnosis of brain myelin changes. We investigated glutamate level changes in the cerebral white matter of a rat model of cuprizone-administered demyelination and remyelination using GluCEST. METHOD: We used a 7 T pre-clinical magnetic resonance imaging (MRI) system. The rats were divided into the normal control (CTRL), cuprizone-administered demyelination (CPZDM), and remyelination (CPZRM) groups. GluCEST data were analyzed using the conventional magnetization transfer ratio asymmetry in the corpus callosum. Immunohistochemistry and transmission electron microscopy analyses were also performed to investigate the myelinated axon changes in each group. RESULTS: The quantified GluCEST signals differed significantly between the CPZDM and CTRL groups (-7.25 ± 1.42% vs. -2.84 ± 1.30%; p = 0.001). The increased GluCEST signals in the CPZDM group decreased after remyelination (-6.52 ± 1.95% in CPZRM) to levels that did not differ significantly from those in the CTRL group (p = 0.734). CONCLUSION: The apparent temporal signal changes in GluCEST imaging during demyelination and remyelination demonstrated the potential usefulness of GluCEST imaging as a tool to monitor the myelination process.

Aryl hydrocarbon receptor antagonism before reperfusion attenuates cerebral ischaemia/reperfusion injury in rats.

Aryl hydrocarbon receptor (AhR) antagonism can mitigate cellular damage associated with cerebral ischaemia and reperfusion (I/R) injury. This study investigated the neuroprotective effects of AhR antagonist administration before reperfusion in a rat stroke model and influence of the timing of AhR antagonist administration on its neuroprotective effects. Magnetic resonance imaging (MRI) was performed at baseline, immediately after, and 3, 8, and 24 h after ischaemia in the sham, control (I/R injury), TMF10 (trimethoxyflavone [TMF] administered 10 min post-ischaemia), and TMF50 (TMF administered 50 min post-ischaemia) groups. The TMF treatment groups had significantly fewer infarcts than the control group. At 24 h, the relative apparent diffusion coefficient values of the ischaemic core and peri-infarct region were significantly higher and relative T2 values were significantly lower in the TMF10 groups than in the control group. The TMF treatment groups showed significantly fewer terminal deoxynucleotidyl transferase dUTP nick-end labelling positive (+) cells (%) in the peri-infarct region than the control group. This study demonstrated that TMF treatment 10 or 50 min after ischaemia alleviated brain damage. Furthermore, the timing of AhR antagonist administration affected the inhibition of cellular or vasogenic oedema formation caused by a transient ischaemic stroke.