Search Results (8)

Therapeutic antibodies for reducing Aβ plaque load in Alzheimer’s disease (AD) is currently making rapid progress. The diagnostic imaging of Aβ plaque load in AD has been underway and is now used in clinical studies. Here, we report our preliminary findings on imaging a therapeutic antibody, Lecanemab, in a postmortem AD brain anterior cingulate. [¹²⁵I]5-iodo-3-pyridinecarboxamido-Lecanemab ([¹²⁵I]IPC-Lecanemab) was prepared by coupling N-succinimidyl-5-([¹²⁵I]iodo)-3-pyridinecarboxylate with Lecanemab in modest yields. The distinct binding of [¹²⁵I]IPC-Lecanemab to Aβ-rich regions in postmortem human AD brains was higher in grey matter (GM) containing Aβ plaques compared to white matter (WM) (GM/WM was 1.6). Anti-Aβ immunostaining was correlated with [¹²⁵I]IPC-Lecanemab regional binding in the postmortem AD human brains. [¹²⁵I]IPC-Lecanemab binding was consistent with the binding of Aβ small molecules, [¹⁸F]flotaza and [¹²⁵I]IBETA, in the same subjects. [¹⁸F]Flotaza and [¹²⁵I]IBETA, however, exhibited significantly higher GM/WM ratios (>20) compared to [¹²⁵I]IPC-Lecanemab. Our results suggest that radiolabeled [¹²⁵I]IPC-Lecanemab retains the ability to bind to Aβ in human AD and may therefore be useful as a PET imaging radiotracer when labeled as [¹²⁴I]IPC-Lecanemab. The ability to directly visualize in vivo a promising therapeutic antibody for AD may be useful in treatment planning and dosing and could be complimentary to small-molecule diagnostic imaging to assess outcomes of therapeutic interventions. Full article

MEMS (micro-electro-mechanical system) gyroscopes and accelerometers are used in several applications. They are very popular due to their small size, low price, and accessibility. The design of MEMS accelerometers enables the measurement of vibrations, with frequencies from tenths of hertz to even 1 kHz. MEMS gyroscopes can be applied to measure angular rates, and indirectly also angular oscillations with frequencies similar to accelerometers. Despite significant stochastic errors, MEMS sensors are used not only in popular domestic appliances (e.g., smartphones) but also in safety-critical units, such as aeronautical attitude and heading reference systems (AHRSs). In engineering, methods of stochastic properties analysis are important tools for sensor selection, verification, and the design of measurement algorithms. In this article, three methods used for the analysis of stochastic properties of sensors are presented and comparative analyses are shown. The applied measurement frequencies (1 kHz) were much higher than those typically found in MEMS sensor applications. Additionally, an exemplary analysis of temperature drift frequency, as well as the possibility for the synthesis of complementary filter parameters with the use of the described methods, is shown. Assessment of the stochastic properties of MEMS accelerometers and gyroscopes was performed under both constant and variable temperature conditions (during warm-up after switching on) with the use of classic methods, such as power spectral density (PSD) and Allan variance (AV), as well as the less known but very promising generalized method of wavelet moments (GMWM). Full article

Pain is considered an unpleasant perceptual experience associated with actual or potential somatic and visceral harm. Human subjects have different sensitivity to painful stimulation, which may be related to different painful response pattern. Excellent studies using functional magnetic resonance imaging (fMRI) have found the effect of the functional organization of white matter (WM) on the descending pain modulatory system, which suggests that WM function is feasible during pain modulation. In this study, 26 pain sensitive (PS) subjects and 27 pain insensitive (PIS) subjects were recruited based on cold pressor test. Then, all subjects underwent the cold bottle test (CBT) in normal (26 degrees temperature stimulating) and cold (8 degrees temperature stimulating) conditions during fMRI scan, respectively. WM functional networks were obtained using K-means clustering, and the functional connectivity (FC) was assessed among WM networks, as well as gray matter (GM)–WM networks. Through repeated measures ANOVA, decreased FC was observed between the GM–cerebellum network and the WM–superior temporal network, as well as the WM–sensorimotor network in the PS group under the cold condition, while this difference was not found in PIS group. Importantly, the changed FC was positively correlated with the state and trait anxiety scores, respectively. This study highlighted that the WM functional network might play an integral part in pain processing, and an altered FC may be related to the descending pain modulatory system. Full article

The gray matter/white matter (GM/WM) boundary of the brain is vulnerable to shear strain associated with mild traumatic brain injury (mTBI). It is, however, unknown whether GM/WM microstructure is associated with long-term outcomes following mTBI. The diffusion and structural MRI data of 278 participants between 18 and 65 years of age with and without military background from the Department of Defense INTRuST study were analyzed. Fractional anisotropy (FA) was extracted at the GM/WM boundary across the brain and for each lobe. Additionally, two conventional analytic approaches were used: whole-brain deep WM FA (TBSS) and whole-brain cortical thickness (FreeSurfer). ANCOVAs were applied to assess differences between the mTBI cohort (n = 147) and the comparison cohort (n = 131). Associations between imaging features and post-concussive symptom severity, and functional and cognitive impairment were investigated using partial correlations while controlling for mental health comorbidities that are particularly common among military cohorts and were present in both the mTBI and comparison group. Findings revealed significantly lower whole-brain and lobe-specific GM/WM boundary FA (p < 0.011), and deep WM FA (p = 0.001) in the mTBI cohort. Whole-brain and lobe-specific GM/WM boundary FA was significantly negatively correlated with post-concussive symptoms (p < 0.039), functional (p < 0.016), and cognitive impairment (p < 0.049). Deep WM FA was associated with functional impairment (p = 0.002). Finally, no significant difference was observed in cortical thickness, nor between cortical thickness and outcome (p > 0.05). Findings from this study suggest that microstructural alterations at the GM/WM boundary may be sensitive markers of adverse long-term outcomes following mTBI. Full article

Borderline personality disorder (BPD) is a severe personality disorder whose neural bases are still unclear. Indeed, previous studies reported inconsistent findings concerning alterations in cortical and subcortical areas. In the present study, we applied for the first time a combination of an unsupervised machine learning approach known as multimodal canonical correlation analysis plus joint independent component analysis (mCCA+jICA), in combination with a supervised machine learning approach known as random forest, to possibly find covarying gray matter and white matter (GM-WM) circuits that separate BPD from controls and that are also predictive of this diagnosis. The first analysis was used to decompose the brain into independent circuits of covarying grey and white matter concentrations. The second method was used to develop a predictive model able to correctly classify new unobserved BPD cases based on one or more circuits derived from the first analysis. To this aim, we analyzed the structural images of patients with BPD and matched healthy controls (HCs). The results showed that two GM-WM covarying circuits, including basal ganglia, amygdala, and portions of the temporal lobes and of the orbitofrontal cortex, correctly classified BPD against HC. Notably, these circuits are affected by specific child traumatic experiences (emotional and physical neglect, and physical abuse) and predict symptoms severity in the interpersonal and impulsivity domains. These results support that BPD is characterized by anomalies in both GM and WM circuits related to early traumatic experiences and specific symptoms. Full article

Regardless of whether the global navigation satellite system (GNSS)/inertial navigation system (INS) is integrated or the INS operates independently during GNSS outages, the stochastic error of the inertial sensor has an important impact on the navigation performance. The structure of stochastic error in low-cost inertial sensors is quite complex; therefore, it is difficult to identify and separate errors in the spectral domain using classical stochastic error methods such as the Allan variance (AV) method and power spectral density (PSD) analysis. However, a recently proposed estimation, based on generalized wavelet moment estimation (GMWM), is applied to the stochastic error modeling of inertial sensors, giving significant advantages. Focusing on the online implementation of GMWM and its integration within a general navigation filter, this paper proposes an algorithm for online stochastic error calibration of inertial sensors in urban cities. We further develop the autonomous stochastic error model by constructing a complete stochastic error model and determining model ranking criterion. Then, a detecting module is designed to work together with the autonomous stochastic error model as feedback for the INS/GNSS integration. Finally, two experiments are conducted to compare the positioning performance of this algorithm with other classical methods. The results validate the capability of this algorithm to improve navigation accuracy and achieve the online realization of complex stochastic models. Full article

Background: Chiari Type I malformation (CM-I) is defined as the migration of cerebellar tonsils from the foramen magnum in the caudal direction and is characterized by the disproportion of the neural structures. The aim of this study was to investigate the brain volume differences between CM-I patients and normal population using a comparative volumetric analysis. Methods: 140 patients with CM-I and 140 age- and sex-matched healthy controls were included in this study. The magnetic resonance imaging (MRI) data of both groups were analyzed with an automated MRI brain morphometry system. Total intracranial, cerebrum, cerebellum, brainstem, cerebrospinal fluid (CSF), and lateral ventricle volumes as well as cerebrum and cerebellum gray/white matter (GM/WM) volumes were measured. Statistical analysis was performed. Results: Both total CSF and lateral ventricle volumes and volume percentages (Pct) were found significantly higher in CM-I patients compared to the control group. However, there were significant decreases in cerebrum and cerebellum volume Pct in CM-I patients. Although there were no significant differences in cerebrum WM volumes and volume Pct, cerebrum GM volume Pct were found to be significantly lower in CM-I patients. Conclusions: Revealing the increased CSF and lateral ventricle volume, and volume Pct supported concomitant ventricular enlargement and hydrocephalus in some CM-I patients. Decreased cerebrum GM volume Pct compared to the control group might be the underlying factor of some cortical dysfunctions in CM-I patients. Full article

The ATP-binding cassette transporter member A1 (ABCA1) and apolipoprotein E (ApoE) are major cholesterol transporters that play important roles in cholesterol homeostasis in the brain. Previous research demonstrated that specific deletion of brain-ABCA1 (ABCA1^−B/−B) reduced brain grey matter (GM) and white matter (WM) density in the ischemic brain and decreased functional outcomes after stroke. However, the downstream molecular mechanism underlying brain ABCA1-deficiency-induced deficits after stroke is not fully understood. Adult male ABCA1^−B/−B and ABCA1-floxed control mice were subjected to distal middle-cerebral artery occlusion and were intraventricularly infused with artificial mouse cerebrospinal fluid as vehicle control or recombinant human ApoE2 into the ischemic brain starting 24 h after stroke for 14 days. The ApoE/apolipoprotein E receptor 2 (ApoER2)/high-density lipoprotein (HDL) levels and GM/WM remodeling and functional outcome were measured. Although ApoE2 increased brain ApoE/HDL levels and GM/WM density, negligible functional improvement was observed in ABCA1-floxed-stroke mice. ApoE2-administered ABCA1^−B/−B stroke mice exhibited elevated levels of brain ApoE/ApoER2/HDL, increased GM/WM density, and neurogenesis in both the ischemic ipsilateral and contralateral brain, as well as improved neurological function compared with the vehicle-control ABCA1^−B/−B stroke mice 14 days after stroke. Ischemic lesion volume was not significantly different between the two groups. In vitro supplementation of ApoE2 into primary cortical neurons and primary oligodendrocyte-progenitor cells (OPCs) significantly increased ApoER2 expression and enhanced cholesterol uptake. ApoE2 promoted neurite outgrowth after oxygen-glucose deprivation and axonal outgrowth of neurons, and increased proliferation/survival of OPCs derived from ABCA1^−B/−B mice. Our data indicate that administration of ApoE2 minimizes the adverse effects of ABCA1 deficiency after stroke, at least partially by promoting cholesterol traffic/redistribution and GM/WM remodeling via increasing the ApoE/HDL/ApoER2 signaling pathway. Full article