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The blood–brain barrier (BBB) plays important roles in the maintenance of brain homeostasis. Its main role includes three kinds of functions: (1) to protect the central nervous system from blood-borne toxins and pathogens; (2) to regulate the exchange of substances between the brain parenchyma and capillaries; and (3) to clear metabolic waste and other neurotoxic compounds from the central nervous system into meningeal lymphatics and systemic circulation. Physiologically, the BBB belongs to the glymphatic system and the intramural periarterial drainage pathway, both of which are involved in clearing interstitial solutes such as β-amyloid proteins. Thus, the BBB is believed to contribute to preventing the onset and progression for Alzheimer’s disease. Measurements of BBB function are essential toward a better understanding of Alzheimer’s pathophysiology to establish novel imaging biomarkers and open new avenues of interventions for Alzheimer’s disease and related dementias. The visualization techniques for capillary, cerebrospinal, and interstitial fluid dynamics around the neurovascular unit in living human brains have been enthusiastically developed. The purpose of this review is to summarize recent BBB imaging developments using advanced magnetic resonance imaging technologies in relation to Alzheimer’s disease and related dementias. First, we give an overview of the relationship between Alzheimer’s pathophysiology and BBB dysfunction. Second, we provide a brief description about the principles of non-contrast agent-based and contrast agent-based BBB imaging methodologies. Third, we summarize previous studies that have reported the findings of each BBB imaging method in individuals with the Alzheimer’s disease continuum. Fourth, we introduce a wide range of Alzheimer’s pathophysiology in relation to BBB imaging technologies to advance our understanding of the fluid dynamics around the BBB in both clinical and preclinical settings. Finally, we discuss the challenges of BBB imaging techniques and suggest future directions toward clinically useful imaging biomarkers for Alzheimer’s disease and related dementias.

Background Mounting evidence suggests that the blood-brain barrier (BBB) plays an important role in the regulation of brain iron homeostasis in normal brain development, but these imaging profiles remain to be elucidated. We aimed to establish a relationship between brain iron dynamics and BBB function during childhood using a combined quantitative magnetic resonance imaging (MRI) to depict both physiological systems along developmental trajectories. Methods In this single-center prospective study, consecutive outpatients, 2–180 months of age, who underwent brain MRI (3.0-T scanner; Ingenia; Philips) between January 2020 and January 2021, were included. Children with histories of preterm birth or birth defects, abnormalities on MRI, and diagnoses that included neurological diseases during follow-up examinations through December 2022 were excluded. In addition to clinical MRI, quantitative susceptibility mapping (QSM; iron deposition measure) and diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL; BBB function measure) were acquired. Atlas-based analyses for QSM and DP-pCASL were performed to investigate developmental trajectories of regional brain iron deposition and BBB function and their relationships. Results A total of 78 children (mean age, 73.8 months ± 61.5 [SD]; 43 boys) were evaluated. Rapid magnetic susceptibility progression in the brain (Δsusceptibility value) was observed during the first two years (globus pallidus, 1.26 ± 0.18 [× 10 − 3 ppm/month]; substantia nigra, 0.68 ± 0.16; thalamus, 0.15 ± 0.04). The scattergram between the Δsusceptibility value and the water exchange rate across the BBB ( k w ) divided by the cerebral blood flow was well fitted to the sigmoidal curve model, whose inflection point differed among each deep gray-matter nucleus (globus pallidus, 2.96–3.03 [mL/100 g] −1 ; substantia nigra, 3.12–3.15; thalamus, 3.64–3.67) in accordance with the regional heterogeneity of brain iron accumulation. Conclusions The combined quantitative MRI study of QSM and DP-pCASL for pediatric brains demonstrated the relationship between brain iron dynamics and BBB function during childhood. Trial registration UMIN Clinical Trials Registry identifier: UMIN000039047, registered January 6, 2020.

Coronavirus disease 2019 (COVID-19) pandemic has posed a major public health crisis all over the world. The role of chest imaging, especially computed tomography (CT), has evolved during the pandemic paralleling the accumulation of scientific evidence. In the early stage of the pandemic, the performance of chest imaging for COVID-19 has widely been debated especially in the context of comparison to real-time reverse transcription polymerase chain reaction. Current evidence is against the use of chest imaging for routine screening of COVID-19 contrary to the initial expectations. It still has an integral role to play, however, in its work up and staging, especially when assessing complications or disease progression. Chest CT is gold standard imaging modality for COVID-19 pneumonia; in some situations, chest X-ray or ultrasound may be an effective alternative. The most important role of radiologists in this context is to be able to identify those patients at greatest risk of imminent clinical decompensation by learning to stratify cases of COVID-19 on the basis of radiologic imaging in the most efficient and timely fashion possible. The present availability of multiple and more refined CT grading systems and classification is now making this task easier and thereby contributing to the recent improvements achieved in COVID-19 treatment and outcomes. In this article, evidence of chest imaging regarding diagnosis, management and monitoring of COVID-19 will be chronologically reviewed.

Objective The Centiloid (CL) scale is a standardized measure for quantifying amyloid deposition in amyloid positron emission tomography (PET) imaging. We aimed to assess the agreement among 3 CL calculation methods: CapAIBL, VIZCalc, and Amyquant. Methods This study included 192 participants (mean age: 71.5 years, range: 50–87 years), comprising 55 with Alzheimer’s disease, 65 with mild cognitive impairment, 13 with non-Alzheimer's dementia, and 59 cognitively normal participants. All the participants were assessed using the three CL calculation methods. Spearman’s rank correlation, linear regression, Friedman tests, Wilcoxon signed-rank tests, and Bland–Altman analysis were employed to assess data correlations, linear associations, method differences, and systematic bias, respectively. Results Strong correlations (rho = 0.99, p  < .001) were observed among the CL values calculated using the three methods. Scatter plots and regression lines visually confirmed these strong correlations and met the validation criteria. Despite the robust correlations, a significant difference in CL value between CapAIBL and Amyquant was observed (36.1 ± 39.7 vs. 34.9 ± 39.4; p  < .001). In contrast, no significant differences were found between CapAIBL and VIZCalc or between VIZCalc and Amyquant. The Bland–Altman analysis showed no observable systematic bias between the methods. Conclusions The study demonstrated strong agreement among the three methods for calculating CL values. Despite minor variations in the absolute values of the Centiloid scores obtained using these methods, the overall agreement suggests that they are interchangeable.

PurposeTo explore the CT findings and pneumonnia progression pattern of the Alpha and Delta variants of SARS-CoV-2 by comparing them with the pre-existing wild type.MethodIn this retrospective comparative study, a total of 392 patients with COVID-19 were included: 118 patients with wild type (70 men, 56.8 ± 20.7 years), 137 with Alpha variant (93 men, 49.4 ± 17.0 years), and 137 with Delta variant (94 men, 45.4 ± 12.4). Chest CT evaluation included opacities and repairing changes as well as lesion distribution and laterality. Chest CT severity score was also calculated. These parameters were statistically compared across the variants.ResultsGround glass opacity (GGO) with consolidation and repairing changes were more frequent in the order of Delta variant, Alpha variant, and wild type throughout the disease course. Delta variant showed GGO with consolidation more conspicuously than did the other two on days 1–4 (vs. wild type, Bonferroni corrected p = 0.01; vs. Alpha variant, Bonferroni corrected p = 0.003) and days 5–8 (vs. wild type, Bonferroni corrected p < 0.001; vs. Alpha variant, Bonferroni corrected-p = 0.003). Total lung CT severity scores of Delta variant were higher than those of wild type on days 1–4 and 5–8 (Bonferroni corrected p = 0.01 and Bonferroni corrected p = 0.005, respectively) and that of Alpha variant on days 1–4 (Bonferroni corrected p = 0.002). There was no difference in the CT findings between wild type and Alpha variant.ConclusionsPneumonia progression of Delta variant may be more rapid and severe in the early stage than in the other two.

Myotonic dystrophy type 1 (DM1) is a multisystem autosomal dominant disorder primarily characterized by myotonia and distal muscle weakness. Central nervous system (CNS) involvement, including cognitive, executive, and emotional dysfunctions, is increasingly being recognized; however, language impairment as an initial presentation is rare. A 50-year-old right-handed woman with a six-month history of progressive word-finding difficulty, vague speech, and social withdrawal was referred for evaluation. Neurological examination revealed distal muscle atrophy (grip strength: 5 kg right, 8 kg left) without overt dysarthria or dysphagia, and intact reflexes and coordination. Neuropsychological testing revealed fluent spontaneous speech with anomia, semantic paraphasia, impaired comprehension of longer sentences, and surface dyslexia/agraphia (Mini-Mental State Examination-Japanese: 22/30, Frontal Assessment Battery: 8/18, Raven's Colored Progressive Matrices: 28/36, Montreal Cognitive Assessment-Japanese: 21/30). Brain magnetic resonance imaging revealed left-sided frontotemporal and limbic atrophy, and Tc-ethyl cysteinate dimer single-photon emission computed tomography showed a corresponding left-dominant hypoperfusion. Amyloid positron emission tomography (PET) scan results were negative. Two weeks later, percussion and grip myotonia emerged. Genetic analysis revealed a cytosine-thymine-guanine repeat expansion (~1500 repeats) in the myotonic protein kinase 1 gene, confirming the diagnosis of DM1. The patient's semantic-variant primary progressive aphasia-like profile (impaired semantic processing with preserved fluency) and frontotemporal imaging findings were consistent with rare CNS phenotypes reported in DM1. Previous studies have described frontotemporal atrophy, hypoperfusion, and cognitive/emotional changes in DM1. Negative amyloid PET excluded Alzheimer-related primary progressive aphasia. The subsequent detection of myotonia and a positive family history were key to diagnosis. We conclude that this case expands the clinical spectrum of DM1 to include progressive aphasia as an initial manifestation. Clinicians should maintain a high suspicion of neuromuscular disorders and actively pursue targeted genetic testing when atypical aphasia symptoms are accompanied by distal muscle atrophy.

Background The functional connectivity of the default mode network (DMN) decreases in patients with Alzheimer’s disease (AD) as well as in patients with type 2 diabetes mellitus (T2DM). Altered functional connectivity of the DMN is associated with cognitive impairment. T2DM is a known cause of cognitive dysfunction and dementia in the elderly, and studies have established that T2DM is a risk factor for AD. In addition, recent studies with positron emission tomography demonstrated that increased plasma glucose levels decrease neuronal activity, especially in the precuneus/posterior cingulate cortex (PC/PCC), which is the functional core of the DMN. These findings prompt the question of how increased plasma glucose levels decrease neuronal activity in the PC/PCC. Given the association among DMN, AD, and T2DM, we hypothesized that increased plasma glucose levels decrease the DMN functional connectivity, thus possibly reducing PC/PCC neuronal activity. We conducted this study to test this hypothesis. Results Twelve young, healthy participants without T2DM and insulin resistance were enrolled in this study. Each participant underwent resting-state functional magnetic resonance imaging in both fasting and glucose loading conditions to evaluate the DMN functional connectivity. The results showed that the DMN functional connectivity in the PC/PCC was significantly lower in the glucose loading condition than in the fasting condition ( P  = 0.014). Conclusions Together with previous findings, the present results suggest that decreased functional connectivity of the DMN is possibly responsible for reduced PC/PCC neuronal activity in healthy individuals with increased plasma glucose levels.

Objective The purpose of this study was to validate the concordance of visual ratings of [18F] flutemetamol amyloid positron emission tomography (PET) images and to investigate the correlation between the agreement of each rater and the Centiloid (CL) scale. Methods A total of 192 participants, clinically classified as cognitively normal (CN) ( n  = 59), mild cognitive impairment (MCI) ( n  = 65), Alzheimer’s disease (AD) ( n  = 55), or non-AD dementia ( n  = 13), participated in this study. Three experts conducted visual ratings of the amyloid PET images for all 192 patients, assigning a confidence level to each rating on a three-point scale (certain, probable, or neither). The positive or negative determination of amyloid PET results was made by majority vote. The CL value was calculated using the CapAIBL pipeline. Results Overall, 101 images were determined to be positive, and 91 images were negative. Of the 101 positive images, the three raters were in complete agreement for 92 images and in disagreement for 9 images. Of the 91 negative images, the three raters were in complete agreement for 75 images and in disagreement for 16 images. Interrater reliability among the three experts was particularly high, with both Fleiss’ kappa and Conger’s kappa measuring 0.83 (0.76–0.89). The CL values of the unanimous positive group were significantly greater than those of the other groups, whereas the CL values of the unanimous negative group were significantly lower than those of the other groups. Images with rater disagreement had intermediate CLs. In cases with a high confidence level, the positive or negative visual ratings were in almost complete agreement. However, as confidence levels decreased, experts’ visual ratings became more variable. The lower the confidence level was, the greater the number of cases with disagreement in the visual ratings. Conclusion Three experts independently rated 192 amyloid PET images, achieving a high level of interrater agreement. However, in patients with intermediate amyloid accumulation, visual ratings varied. Therefore, determining positive and negative decisions in these patients should be performed with caution.