Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer's disease.

The associations of synaptic loss with amyloid-ß (Aß) and tau pathology measured by positron emission tomography (PET) and plasma analysis in Alzheimer's disease (AD) patients are unknown. Seventy-five participants, including 26 AD patients, 19 mild cognitive impairment (MCI) patients, and 30 normal controls (NCs), underwent [18F]SynVesT-1 PET/MR scans to assess synaptic density and [18F]florbetapir and [18F]MK6240 PET/CT scans to evaluate Aß plaques and tau tangles. Among them, 19 AD patients, 12 MCI patients, and 29 NCs had plasma Aß42/40 and p-tau181 levels measured by the Simoa platform. Twenty-three individuals, 6 AD patients, 4 MCI patients, and 13 NCs, underwent [18F]SynVesT-1 PET/MRI and [18F]MK6240 PET/CT scans during a one-year follow-up assessment. The associations of Aß and tau pathology with cross-sectional and longitudinal synaptic loss were investigated using Pearson correlation analyses, generalized linear models and mediation analyses. AD patients exhibited lower synaptic density than NCs and MCI patients. In the whole cohort, global Aß deposition was associated with synaptic loss in the medial (r = -0.431, p < 0.001) and lateral (r = -0.406, p < 0.001) temporal lobes. Synaptic density in almost all regions was related to the corresponding regional tau tangles independent of global Aß deposition in the whole cohort and stratified groups. Synaptic density in the medial and lateral temporal lobes was correlated with plasma Aß42/40 (r = 0.300, p = 0.020/r = 0.289, p = 0.025) and plasma p-tau 181 (r = -0.412, p = 0.001/r = -0.529, p < 0.001) levels in the whole cohort. Mediation analyses revealed that tau tangles mediated the relationship between Aß plaques and synaptic density in the whole cohort. Baseline tau pathology was positively associated with longitudinal synaptic loss. This study suggested that tau burden is strongly linked to synaptic density independent of Aß plaques, and also can predict longitudinal synaptic loss.

Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment.

INTRODUCTION: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD). METHODS: Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18F]SynVesT-1 and [18F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability. The associations between mGluR5 availability and synaptic density were examined. A mediation analysis was performed to investigate the possible mediating effects of mGluR5 availability and synaptic loss on the relationship between amyloid deposition and cognition. RESULTS: CI patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and cognition. CONCLUSIONS: Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked. HIGHLIGHTS: Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition. With further research, modulating mGluR5 availability might be a potential therapeutic strategy for improving synaptic function in AD.

Predicting the Onset of Ischemic Stroke With Fast High-Resolution 3D MR Spectroscopic Imaging.

BACKGROUND: Neurometabolite concentrations provide a direct index of infarction progression in stroke. However, their relationship with stroke onset time remains unclear. PURPOSE: To assess the temporal dynamics of N-acetylaspartate (NAA), creatine, choline, and lactate and estimate their value in predicting early (<6 hours) vs. late (6-24 hours) hyperacute stroke groups. STUDY TYPE: Cross-sectional cohort. POPULATION: A total of 73 ischemic stroke patients scanned at 1.8-302.5 hours after symptom onset, including 25 patients with follow-up scans. FIELD STRENGTH/SEQUENCE: A 3 T/magnetization-prepared rapid acquisition gradient echo sequence for anatomical imaging, diffusion-weighted imaging and fluid-attenuated inversion recovery imaging for lesion delineation, and 3D MR spectroscopic imaging (MRSI) for neurometabolic mapping. ASSESSMENT: Patients were divided into hyperacute (0-24 hours), acute (24 hours to 1 week), and subacute (1-2 weeks) groups, and into early (<6 hours) and late (6-24 hours) hyperacute groups. Bayesian logistic regression was used to compare classification performance between early and late hyperacute groups by using different combinations of neurometabolites as inputs. STATISTICAL TESTS: Linear mixed effects modeling was applied for group-wise comparisons between NAA, creatine, choline, and lactate. Pearson's correlation analysis was used for neurometabolites vs. time. P < 0.05 was considered statistically significant. RESULTS: Lesional NAA and creatine were significantly lower in subacute than in acute stroke. The main effects of time were shown on NAA (F = 14.321) and creatine (F = 12.261). NAA was significantly lower in late than early hyperacute patients, and was inversely related to time from symptom onset across both groups (r = -0.440). The decrease of NAA and increase of lactate were correlated with lesion volume (NAA: r = -0.472; lactate: r = 0.366) in hyperacute stroke. Discrimination was improved by combining NAA, creatine, and choline signals (area under the curve [AUC] = 0.90). DATA CONCLUSION: High-resolution 3D MRSI effectively assessed the neurometabolite changes and discriminated early and late hyperacute stroke lesions. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Fast high-resolution metabolic imaging of acute stroke with 3D magnetic resonance spectroscopy.

Impaired oxygen and cellular metabolism is a hallmark of ischaemic injury in acute stroke. Magnetic resonance spectroscopic imaging (MRSI) has long been recognized as a potentially powerful tool for non-invasive metabolic imaging. Nonetheless, long acquisition time, poor spatial resolution, and narrow coverage have limited its clinical application. Here we investigated the feasibility and potential clinical utility of rapid, high spatial resolution, near whole-brain 3D metabolic imaging based on a novel MRSI technology. In an 8-min scan, we simultaneously obtained 3D maps of N-acetylaspartate and lactate at a nominal spatial resolution of 2.0 × 3.0 × 3.0 mm3 with near whole-brain coverage from a cohort of 18 patients with acute ischaemic stroke. Serial structural and perfusion MRI was used to define detailed spatial maps of tissue-level outcomes against which high-resolution metabolic changes were evaluated. Within hypoperfused tissue, the lactate signal was higher in areas that ultimately infarcted compared with those that recovered (P < 0.0001). Both lactate (P < 0.0001) and N-acetylaspartate (P < 0.001) differed between infarcted and other regions. Within the areas of diffusion-weighted abnormality, lactate was lower where recovery was observed compared with elsewhere (P < 0.001). This feasibility study supports further investigation of fast high-resolution MRSI in acute stroke.

Use of Compressed Sensing Accelerated, Low-Velocity Encoded, Isotropic Resolution, Phase Contrast Magnetic Resonance Angiography for SEEG Electrode Implantation.

OBJECTIVE: We assessed the feasibility of using compressed sensing accelerated, low-velocity encoded, isotropic resolution phase contrast (CLIP) magnetic resonance angiography (MRA) for avascular trajectory planning of stereoelectroencephalography. METHODS: Ten healthy subjects (1 woman and 9 men; age, 33.6 ± 9.0 years) and 20 consecutive patients (12 female patients; age, 22 ± 13.6 years) were enrolled in the present study. The healthy subjects underwent CLIP-MRA, and 3 other phase contrast MRA protocols with conventional parallel imaging (PI) acceleration, including low resolution with twofold PI (PI2), high resolution (HR) with fivefold PI (PI5), and HR-PI2. The patients underwent CLIP-MRA and computed tomography angiography (CTA). The image qualities were evaluated. The numbers and locations of trajectory-vessel conflict detected using CLIP-MRA were noted. RESULTS: With similar scan durations, CLIP-MRA achieved higher spatial resolution compared with low resolution with PI2 and detected significantly more branches compared with HR-PI5. With the same spatial resolution, the signal/noise and contrast/noise ratios of CLIP-MRA were higher than those with HR-PI2 with a shorter scan duration. For the 12 adult patients (10 female patients; 28.8 ± 12.7 years), CLIP-MRA had better signal/noise and contrast/noise ratios than CTA. The trajectory had required modification for 14 of the 20 patients (70%), with a proportion of trajectory modification of 10.7% (23 of 215 electrodes). The middle meningeal artery, cortical vessel, and skull vessel were the main vessels with conflict (n = 11, n = 7, and n = 5, respectively). CONCLUSIONS: In the present study, CLIP-MRA provided a clear cortical vascular display noninvasively without intravascular contrast and radiation. The middle meningeal artery and diploic and emissary veins were the main conflict vessels and could be clearly displayed using CLIP-MRA but not CTA.

Advances in microneedle-based therapy for bone disorders.

Bone-related disorders treatment is a serious public health concern, imposing a significant social and economic burden on patients and healthcare systems. Although conventional drug delivery systems have made advances in bone diseases prevention and management, the limited delivery efficiency and convoluted focal environment lead to inadequate drug absorption and lack of specificity to achieve the intended therapeutic impact. Microneedle-based therapy represents an extraordinarily safe and well-tolerable therapeutic approach for treating bone disorders, providing improved efficacy by breaking down the barriers and delivery of therapeutic components to the target sites with programable release profiles in a less invasive manner. Over the past decades, numerous significant achievements in the development of various types of drug-carried microneedles have been made to address the obstacles encountered in the bone-treating procedure, enabling the microneedle-based therapy to take an important step in practical applications. In this light, this review summarizes these remarkable researches in terms of microneedles types and drug delivery strategies, with the goal of demonstrating the benefits of exploiting microneedle-based therapy as a novel strategy for treating bone-related disorders. The remaining challenges and future perspectives are also discussed in the hope of inspiring more efficient and intelligent bone treatment strategies.

Own-Age Effects in a Face-Emotion Recognition Intervention for Children With ASD--Evidence From Eye Movements.

Background: The own-age effect is the phenomenon in which individuals perceive and recognize faces of their own age better than others in terms of cognitive processing. Previous eye movement studies on children with autism spectrum disorders (ASD) have reported that children with ASD have an attentional bias toward own-age faces and own-age scenes. Methods: The present study used own-age faces as the intervention material and examined the application of the own-age effect in the emotional recognition of faces in ASD. The length of the intervention was 12 weeks, and 2 sessions were conducted each week. Results: The results revealed that the own-age face intervention group gazed at children's faces significantly more often than before the intervention, gazed at children's angry faces significantly longer than before the intervention, and gazed at adults' happy faces significantly longer and more often than before the intervention; the other-age faces intervention group did not differ significantly from the preintervention in gazing at children's and adults' faces after the intervention. Conclusion: The results suggest that own-age faces as teaching materials can better promote the emotion recognition ability of children with ASD than other-age faces.

Prediction of Stroke Onset Time With Combined Fast High-Resolution Magnetic Resonance Spectroscopic and Quantitative T2 Mapping.

OBJECTIVE: The purpose of this work is to develop a multispectral imaging approach that combines fast high-resolution 3D magnetic resonance spectroscopic imaging (MRSI) and fast quantitative T2 mapping to capture the multifactorial biochemical changes within stroke lesions and evaluate its potentials for stroke onset time prediction. METHODS: Special imaging sequences combining fast trajectories and sparse sampling were used to obtain whole-brain maps of both neurometabolites (2.0 × 3.0 × 3.0 mm3) and quantitative T2 values (1.9 × 1.9 × 3.0 mm3) within a 9-minute scan. Participants with ischemic stroke at hyperacute (0-24 h, n = 23) or acute (24 h-7d, n = 33) phase were recruited in this study. Lesion N-acetylaspartate (NAA), lactate, choline, creatine, and T2 signals were compared between groups and correlated with patient symptomatic duration. Bayesian regression analyses were employed to compare the predictive models of symptomatic duration using multispectral signals. RESULTS: In both groups, increased T2 and lactate levels, as well as decreased NAA and choline levels were detected within the lesion (all p < 0.001). Changes in T2, NAA, choline, and creatine signals were correlated with symptomatic duration for all patients (all p < 0.005). Predictive models of stroke onset time combining signals from MRSI and T2 mapping achieved the best performance (hyperacute: R2 = 0.438; all: R2 = 0.548). CONCLUSION: The proposed multispectral imaging approach provides a combination of biomarkers that index early pathological changes after stroke in a clinical-feasible time and improves the assessment of the duration of cerebral infarction. SIGNIFICANCE: Developing accurate and efficient neuroimaging techniques to provide sensitive biomarkers for prediction of stroke onset time is of great importance for maximizing the proportion of patients eligible for therapeutic intervention. The proposed method provides a clinically feasible tool for the assessment of symptom onset time post ischemic stroke, which will help guide time-sensitive clinical management.

Treatment and outcome of a patient with low-energy 'Logsplitter' injury.

The low-energy 'Logsplitter' fracture, caused by a sprain or fall, is characterized by an intact or slightly separated inferior tibiofibular joint. Compared with the high-energy 'Logsplitter' fracture, this atypical subtype is rarely seen and is easily missed. Here, the case of a 33-year-old male patient with a fractured right ankle as a result of a sprain during walking is reported. The patient initially received routine surgical treatment comprising internal fixation of the fibular, medial and posterior malleoli. Unexpectedly, post-surgery imaging examinations revealed that the medial clear space of the right ankle had widened to 6 mm, due to incomplete reduction of the lateral malleolus, shortening and rotation of the fibula, and an unreduced avulsion fracture block of the anterior malleolus. A revision surgery was then performed to anatomically reduce and fix the lateral malleolus, as well as the anterior malleolus avulsion fracture. During 5 months following surgery, the patient achieved good fracture union and functional restoration of the right ankle. For this rare injury, the present case demonstrates that complete restoration of the fracture is required to achieve good clinical efficacy.

Reduced Cerebral Blood Flow in Benign Oligemia Relates to Poor Clinical Outcome in Acute Ischemic Stroke Patients.

The imaging of cerebral blow flow (CBF) has shown great promise in predicting the tissue outcome or functional outcome of acute ischemic stroke patients. Arterial spin labeling (ASL) provides a noninvasive tool for quantitative CBF measurement and does not require a contrast agent, which makes it an attractive technology for perfusion imaging in clinical settings. Previous studies have shown the feasibility of using ASL for acute stroke imaging and its potential in stroke outcome prediction. However, the relationship between the tissue-level CBF reduction in hypoperfused region and clinical outcome in acute stroke patients remains not well understood. In this study, we obtained the quantitative measurements of CBF in acute ischemic stroke patients (N = 18) using pseudocontinuous ASL (pCASL) perfusion imaging technology. The tissue-level CBF changes were evaluated and their correlations with patient clinical outcome were explored. Our results showed different CBF values between hypoperfused tissues recruited into infarction and those that survived. Moreover, a significant correlation was found specifically between the CBF reduction in benign oligemia area and patient neurological deficit severity. These findings showed the validity of pCASL perfusion imaging in the assessment of tissue-level CBF information in acute stroke. The association of CBF with patient clinical outcome might provide useful insights in early diagnosis of acute stroke patients.

Bilateral Hearing Loss and Unilateral Cochlear Ossification in a Patient With Chronic Myelogenous Leukemia.

Bilateral sensorineural deafness and unilateral cochlear ossification have rarely been described in patients with chronic myeloid leukemia (CML). A 21-year-old man presented to a hospital with right-sided sudden hearing loss and tinnitus. He was diagnosed with CML. Five days later, sudden hearing loss appeared in the other ear. Abnormality of the right-sided inner ear structure was revealed by preoperative magnetic resonance imaging; honeycomb-like cochlear ossification was observed during cochlear implant surgery in the right ear. The patient's auditory performance exhibited significant improvement after bilateral cochlear implantation in our hospital. Hematological disorders must be considered in patients with sensorineural hearing loss. Cochlear implantation is feasible in patients with CML who exhibit sensorineural deafness, but cochlear ossification should be carefully evaluated by means of preoperative imaging examinations.

Spontaneous rupture of the right quadriceps tendon in a patient undergoing long-term hemodialysis: a case report.

Spontaneous unilateral quadriceps tendon rupture is an uncommon injury that is generally associated with chronic kidney disease and metabolic disorders. The current case involved a 50-year-old man with a painful right knee that he was unable to extend as a result of minor trauma sustained in an accident. Physical examination combined with radiographic and ultrasonographic investigations led to a diagnosis of quadriceps tendon rupture of the right knee. The patient had a 7-year history of hemodialysis for treatment of chronic kidney disease, leading to secondary hyperparathyroidism. He underwent successful tendon repair surgery, and his right knee was immobilized with splints for 6 weeks postoperatively. He gradually resumed full weight bearing and then normal walking.