Direct comparison between 18F-Flortaucipir tau PET and quantitative susceptibility mapping in progressive supranuclear palsy.

PURPOSE: The pattern of flortaucipir tau PET uptake is topographically similar to the pattern of magnetic susceptibility in progressive supranuclear palsy (PSP); both with increased signal in subcortical structures such as the basal ganglia and midbrain, suggesting that they may be closely related. However, their relationship remains unknown since no studies have directly compared these two modalities in the same PSP cohort. We hypothesized that some flortaucipir uptake in PSP is associated with magnetic susceptibility, and hence iron deposition. The aim of this study was to evaluate the regional relationship between flortaucipir uptake and magnetic susceptibility and to examine the effects of susceptibility on flortaucipir uptake in PSP. METHODS: Fifty PSP patients and 67 cognitively normal controls were prospectively recruited and underwent three Tesla MRI and flortaucipir tau PET scans. Quantitative susceptibility maps were reconstructed from multi-echo gradient-echo MRI images. Region of interest (ROI) analysis was performed to obtain flortaucipir and susceptibility values in the subcortical regions. Relationships between flortaucipir and susceptibility signals were evaluated using partial correlation analysis in the subcortical ROIs and voxel-based analysis in the whole brain. The effects of susceptibility on flortaucipir uptake were examined by using the framework of mediation analysis. RESULTS: Both flortaucipir and susceptibility were greater in PSP compared to controls in the putamen, pallidum, subthalamic nucleus, red nucleus, and cerebellar dentate (p<0.05). The ROI-based and voxel-based analyses showed that these two signals were positively correlated in these five regions (r = 0.36-0.59, p<0.05). Mediation analysis showed that greater flortaucipir uptake was partially explained by susceptibility in the putamen, pallidum, subthalamic nucleus, and red nucleus, and fully explained in the cerebellar dentate. CONCLUSIONS: These results suggest that some of the flortaucipir uptake in subcortical regions in PSP is related to iron deposition. These findings will contribute to our understanding of the mechanisms underlying flortaucipir tau PET findings in PSP and other neurodegenerative diseases.

Clinical and neuroimaging characteristics of primary lateral sclerosis with overlapping features of progressive supranuclear palsy.

BACKGROUND AND PURPOSE: Primary lateral sclerosis (PLS) is a neurodegenerative disorder that primarily affects the central motor system. In rare cases, clinical features of PLS may overlap with those of progressive supranuclear palsy (PSP). We investigate neuroimaging features that can help distinguish PLS with overlapping features of PSP (PLS-PSP) from PSP. METHODS: Six patients with PLS-PSP were enrolled between 2019 and 2023. We compared their clinical and neuroimaging characteristics with 18 PSP-Richardson syndrome (PSP-RS) patients and 20 healthy controls. Magnetic resonance imaging, 18F-flortaucipir positron emission tomography (PET), quantitative susceptibility mapping, and diffusion tensor imaging tractography (DTI) were performed to evaluate eight brain regions of interest. Area under the receiver operating characteristic curve (AUROC) was calculated. RESULTS: Five of the six PLS-PSP patients (83.3%) were male. Median age at symptom onset was 61.5 (52.5-63) years, and all had mixed features of PLS and PSP. Volumes of the pallidum, caudate, midbrain, and cerebellar dentate were smaller in PSP-RS than PLS-PSP, providing good discrimination (AUROC = 0.75 for all). The susceptibilities in pallidum, midbrain, and cerebellar dentate were greater in PSP-RS compared to PLS-PSP, providing excellent discrimination (AUROC ≥ 0.90 for all). On DTI, fractional anisotropy (FA) in the posterior limb of the internal capsule from the corticospinal tract was lower in PLS-PSP compared to PSP-RS (AUROC = 0.86), but FA in the superior cerebellar peduncle was lower in PSP-RS (AUROC = 0.95). Pallidum flortaucipir PET uptake was greater in PSP-RS compared to PLS-PSP (AUROC = 0.74). CONCLUSIONS: Regional brain volume, tractography, and magnetic susceptibility, but not tau-PET, are useful in distinguishing PLS-PSP from PSP.

Investigating the feasibility of 18F-flortaucipir PET imaging in the antemortem diagnosis of primary age-related tauopathy (PART): An observational imaging-pathological study.

INTRODUCTION: Primary age-related tauopathy (PART) is characterized by neurofibrillary tangles and minimal ß-amyloid deposition, diagnosed postmortem. This study investigates 18F-flortaucipir (FTP) PET imaging for antemortem PART diagnosis. METHODS: We analyzed FTP PET scans from 50 autopsy-confirmed PART and 13 control subjects. Temporal lobe uptake was assessed both qualitatively and quantitatively. Demographic and clinicopathological characteristics and voxel-level uptake using SPM12 were compared between FTP-positive and FTP-negative cases. Intra-reader reproducibility was evaluated with Krippendorff's alpha. RESULTS: Minimal/mild and moderate FTP uptake was seen in 32% of PART cases and 62% of controls, primarily in the left inferior temporal lobe. No demographic or clinicopathological differences were found between FTP-positive and FTP-negative cases. High intra-reader reproducibility (α = 0.83) was noted. DISCUSSION: FTP PET imaging did not show a specific uptake pattern for PART diagnosis, indicating that in vivo PART identification using FTP PET is challenging. Similar uptake in controls suggests non-specific uptake in PART. HIGHLIGHTS: 18F-flortaucipir (FTP) PET scans were analyzed for diagnosing PART antemortem. 32% of PART cases had minimal/mild FTP uptake in the left inferior temporal lobe. Similar to PART FTP uptake was found in 62% of control subjects. No specific uptake pattern was found, challenging in vivo PART diagnosis.

Magnetic Susceptibility in Progressive Supranuclear Palsy Variants, Parkinson's Disease, and Corticobasal Syndrome.

BACKGROUND: Previous studies have shown that magnetic susceptibility is increased in several subcortical regions in progressive supranuclear palsy (PSP). However, it is still unclear how subcortical and cortical susceptibilities vary across different PSP variants, Parkinson's disease (PD), and corticobasal syndrome (CBS). OBJECTIVE: This study aims to clarify the susceptibility profiles in the subcortical and cortical regions in different PSP variants, PD, and CBS. METHODS: Sixty-four patients, 20 PSP-Richardson syndrome (PSP-RS), 9 PSP-parkinsonism (PSP-P), 7 PSP-progressive gait freezing, 4 PSP-postural instability, 11 PD, and 13 CBS, and 20 cognitively normal control subjects underwent a 3-Tesla magnetic resonance imaging scan to reconstruct quantitative susceptibility maps. Region-of-interest analysis was performed to obtain susceptibility in several subcortical and cortical regions. Bayesian linear mixed effect models were used to estimate susceptibility within group and differences between groups. RESULTS: In the subcortical regions, patients with PSP-RS and PSP-P showed greater susceptibility than control subjects in the pallidum, substantia nigra, red nucleus, and cerebellar dentate (P < 0.05). Patients with PSP-RS also showed greater susceptibility than patients with PSP-progressive gait freezing, PD, and CBS in the red nucleus and cerebellar dentate, and patients with PSP-P showed greater susceptibility than PD in the red nucleus. Patients with PSP-postural instability and CBS showed greater susceptibility than control subjects in the pallidum and substantia nigra. No significant differences were observed in any cortical region. CONCLUSIONS: The PSP variants and CBS had different patterns of magnetic susceptibility in the subcortical regions. The findings will contribute to our understanding about iron profiles and pathophysiology of PSP and may provide a potential biomarker to differentiate PSP variants, PD, and CBS. © 2023 International Parkinson and Movement Disorder Society.

A thin-layer solid-phase extraction-liquid film elution technique used for the enrichment of polycyclic aromatic hydrocarbons in water.

In this article, we propose a novel microsolid-phase extraction and elution technique, which we called the thin-layer solid-phase extraction-liquid film elution technique. The thin-layer solid-phase extraction phase is an octadecylsilylated sol gel- coated porous silica thin film prepared on the outer wall of a test tube, which has a larger surface area for the extraction of the target compounds compared to a conventional solid-phase microextraction phase. After optimization of the extraction procedure for five types of polycyclic aromatic hydrocarbons, the liquid film elution technique was investigated. Liquid film elution is an elution technique wherein the compounds extracted into the thin-layer solid-phase extraction phase are eluted using a small volume of solvent film formed around the extraction phase. The results show that the elution can be carried out using 150 µL of eluent. Enrichment factors between 20 and 34 were obtained for polycyclic aromatic hydrocarbons containing more than four aromatic rings in 10 mL aliquots of aqueous samples. Finally, recoveries of 85-112% were obtained for polycyclic aromatic hydrocarbons containing more than four aromatic rings from spiked natural water samples using the thin-layer solid-phase extraction-liquid film elution technique.

Visualization of Venous Compliance of Superficial Veins Using Non-Contact Plethysmography Based on Digital Red-Green-Blue Images.

We propose the visualization of venous compliance (VC) using a digital red-green-blue (RGB) camera. The new imaging method, which transforms RGB values into VC, combines VC evaluation with blood concentration estimation from the RGB values of each pixel. We evaluate a non-contact plethysmography (NCPG) system for VC based on comparisons with conventional strain gauge plethysmography (SPG). We conduct in vivo measurements using both systems and investigate their differences by evaluating the VC. The results show that the two methods measure different blood vessels and that errors caused by interstitial fluid accumulation are negligible for the NCPG system, whereas SPG is influenced by such errors. Additionally, we investigate the relationship between VC and physical activity using NCPG.

Spatial patterns of elevated magnetic susceptibility in progressive apraxia of speech.

PURPOSE: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder affecting the planning or programming of speech. Little is known about its magnetic susceptibility profiles indicative of biological processes such as iron deposition and demyelination. This study aims to clarify (1) the pattern of susceptibility in PAOS patients, (2) the susceptibility differences between the phonetic (characterized by predominance of distorted sound substitutions and additions) and prosodic (characterized by predominance of slow speech rate and segmentation) subtypes of PAOS, and (3) the relationships between susceptibility and symptom severity. METHODS: Twenty patients with PAOS (nine phonetic and eleven prosodic subtypes) were prospectively recruited and underwent a 3 Tesla MRI scan. They also underwent detailed speech, language, and neurological evaluations. Quantitative susceptibility maps (QSM) were reconstructed from multi-echo gradient echo MRI images. Region of interest analysis was conducted to estimate susceptibility coefficients in several subcortical and frontal regions. We compared susceptibility values between PAOS and an age-matched control group and performed a correlation analysis between susceptibilities and an apraxia of speech rating scale (ASRS) phonetic and prosodic feature ratings. RESULTS: The magnetic susceptibility of PAOS was statistically greater than that of controls in subcortical regions (left putamen, left red nucleus, and right dentate nucleus) (p < 0.01, also survived FDR correction) and in the left white-matter precentral gyrus (p < 0.05, but not survived FDR correction). The prosodic patients showed greater susceptibilities than controls in these subcortical and precentral regions. The susceptibility in the left red nucleus and in the left precentral gyrus correlated with the prosodic sub-score of the ASRS. CONCLUSION: Magnetic susceptibility in PAOS patients was greater than controls mainly in the subcortical regions. While larger samples are needed before QSM is considered ready for clinical differential diagnosis, the present study contributes to our understanding of magnetic susceptibility changes and the pathophysiology of PAOS.

A Possible Trifunctional ß-Carotene Synthase Gene Identified in the Draft Genome of Aurantiochytrium sp. Strain KH105.

Labyrinthulomycetes have been regarded as a promising industrial source of xanthophylls, including astaxanthin and canthaxanthin, polyunsaturated fatty acids such as docosahexaenoic acid and docosapentaenoic acid, ω-3 oils, and terpenic hydrocarbons, such as sterols and squalene. A Thraustochytrid, Aurantiochytrium sp. KH105 produces carotenoids, including astaxanthin, with strong antioxidant activity. To gain genomic insights into this capacity, we decoded its 97-Mbp genome and characterized genes for enzymes involved in carotenoid biosynthesis. Interestingly, all carotenogenic genes, as well as other eukaryotic genes, appeared duplicated, suggesting that this strain is diploid. In addition, among the five genes involved in the pathway from geranylgeranyl pyrophosphate to astaxanthin, geranylgeranyl phytoene synthase (crtB), phytoene desaturase (crtI) and lycopene cyclase (crtY) were fused into single gene (crtIBY) with no internal stop codons. Functionality of the trifunctional enzyme, CrtIBY, to catalyze the reaction from geranylgeranyl diphosphate to ß-carotene was confirmed using a yeast assay system and mass spectrometry. Furthermore, analyses of differential gene expression showed characteristic up-regulation of carotenoid biosynthetic genes during stationary and starvation phases under these culture conditions. This suggests genetic engineering events to promote more efficient production of carotenoids. We also showed an occurrence of crtIBY in other Thraustochytrid species.

Neuronal cell patterning on a multi-electrode array for a network analysis platform.

We studied neuronal cell patterning on a commercial multi-electrode array (MEA). We investigated the surface chemical modification of MEA in order to immobilize Poly-D-lysine (PDL) and then to pattern PDL with a photolithographic method using vacuum ultraviolet light (VUV). We have clarified that the PDL layer was not fully decomposed but was partially fragmented by short-time irradiation with VUV, resulting in a change in the cell adhesiveness of the PDL. We succeeded in patterning primary rat cortex cells without manipulating the cells on MEA more than two months. This cell-adhesiveness change induced by VUV can be applied to any immobilized PDL on other kinds of MEA and culturing substrate. We conducted electrophysiological measurements and found that the patterned neuronal cells were sufficiently matured and developed neural networks, demonstrating that our patterning method is useful for a neuronal network analysis platform.

Functional Differences between Global Pre- and Postsynaptic Inhibition in the Drosophila Olfactory Circuit.

The Drosophila antennal lobe is subdivided into multiple glomeruli, each of which represents a unique olfactory information processing channel. In each glomerulus, feedforward input from olfactory receptor neurons (ORNs) is transformed into activity of projection neurons (PNs), which represent the output. Recent investigations have indicated that lateral presynaptic inhibitory input from other glomeruli controls the gain of this transformation. Here, we address why this gain control acts "pre"-synaptically rather than "post"-synaptically. Postsynaptic inhibition could work similarly to presynaptic inhibition with regard to regulating the firing rates of PNs depending on the stimulus intensity. We investigate the differences between pre- and postsynaptic gain control in terms of odor discriminability by simulating a network model of the Drosophila antennal lobe with experimental data. We first demonstrate that only presynaptic inhibition can reproduce the type of gain control observed in experiments. We next show that presynaptic inhibition decorrelates PN responses whereas postsynaptic inhibition does not. Due to this effect, presynaptic gain control enhances the accuracy of odor discrimination by a linear decoder while its postsynaptic counterpart only diminishes it. Our results provide the reason gain control operates "pre"-synaptically but not "post"-synaptically in the Drosophila antennal lobe.

Mechanisms of maximum information preservation in the Drosophila antennal lobe.

We examined the presence of maximum information preservation, which may be a fundamental principle of information transmission in all sensory modalities, in the Drosophila antennal lobe using an experimentally grounded network model and physiological data. Recent studies have shown a nonlinear firing rate transformation between olfactory receptor neurons (ORNs) and second-order projection neurons (PNs). As a result, PNs can use their dynamic range more uniformly than ORNs in response to a diverse set of odors. Although this firing rate transformation is thought to assist the decoder in discriminating between odors, there are no comprehensive, quantitatively supported studies examining this notion. Therefore, we quantitatively investigated the efficiency of this firing rate transformation from the viewpoint of information preservation by computing the mutual information between odor stimuli and PN responses in our network model. In the Drosophila olfactory system, all ORNs and PNs are divided into unique functional processing units called glomeruli. The nonlinear transformation between ORNs and PNs is formed by intraglomerular transformation and interglomerular interaction through local neurons (LNs). By exploring possible nonlinear transformations produced by these two factors in our network model, we found that mutual information is maximized when a weak ORN input is preferentially amplified within a glomerulus and the net LN input to each glomerulus is inhibitory. It is noteworthy that this is the very combination observed experimentally. Furthermore, the shape of the resultant nonlinear transformation is similar to that observed experimentally. These results imply that information related to odor stimuli is almost maximally preserved in the Drosophila olfactory circuit. We also discuss how intraglomerular transformation and interglomerular inhibition combine to maximize mutual information.