Search

Abstract Background To evaluate the clinical performance of two deep learning methods, one utilizing real clinical pairs and the other utilizing simulated datasets, in enhancing image quality for two-dimensional (2D) fast whole-body scintigraphy (WBS). Methods A total of 83 patients with suspected bone metastasis were retrospectively enrolled. All patients underwent single-photon emission computed tomography (SPECT) WBS at speeds of 20 cm/min (1x), 40 cm/min (2x), and 60 cm/min (3x). Two deep learning models were developed to generate high-quality images from real and simulated fast scans, designated 2x-real and 3x-real (images from real fast data) and 2x-simu and 3x-simu (images from simulated fast data), respectively. A 5-point Likert scale was used to evaluate the image quality of each acquisition. Accuracy, sensitivity, specificity, and the area under the curve (AUC) were used to evaluate diagnostic efficacy. Learned perceptual image patch similarity (LPIPS) and the Fréchet inception distance (FID) were used to assess image quality. Additionally, the count-level consistency of WBS was compared between the two models. Results Subjective assessments revealed that the 1x images had the highest general image quality (Likert score: 4.40 ± 0.45). The 2x-real, 2x-simu and 3x-real, 3x-simu images demonstrated significantly better quality than the 2x and 3x images (Likert scores: 3.46 ± 0.47, 3.79 ± 0.55 vs. 2.92 ± 0.41, P 0.05), whereas the diagnostic efficacy for the 3x-real and 3x-simu was better than that for the 3x images (accuracy: 65.1%, 66.35% vs. 59.0%; sensitivity: 63.64%, 63.64% vs. 64.71%; specificity: 66.67%, 69.23% vs. 55.1%. All P

PurposeA method named DECOMPOSE-QSM is developed to decompose bulk susceptibility measured with QSM into sub-voxel paramagnetic and diamagnetic components based on a three-pool complex signal model.MethodsMulti-echo gradient echo signal is modeled as a summation of three weighted exponentials corresponding to three types of susceptibility sources: reference susceptibility, diamagnetic and paramagnetic susceptibility relative to the reference. Paramagnetic component susceptibility (PCS) and diamagnetic component susceptibility (DCS) maps are constructed to represent the sub-voxel compartments by solving for linear and nonlinear parameters in the model.ResultsNumerical forward simulation and phantom validation confirmed the ability of DECOMPOSE-QSM to separate the mixture of paramagnetic and diamagnetic components. The PCS obtained from temperature-variant brainstem imaging follows the Curie's Law, which further validated the model and the solver. Initial in vivo investigation of human brain images showed the ability to extract sub-voxel PCS and DCS sources that produce visually enhanced contrast between brain structures comparing to threshold QSM.

Abstract Background Ribosomal protein S6 kinase 1 (S6K1) is a serine–threonine kinase that has two main isoforms: p70S6K (70-kDa isoform) and p85S6K (85-kDa isoform). p70S6K, with its upstream mammalian target of rapamycin (mTOR), has been shown to be involved in learning and memory and participate in the pathophysiology of Alzheimer’s disease (AD). However, the function of p85S6K has long been neglected due to its high similarity to p70S6k. The role of p85S6K in learning and memory is still largely unknown. Methods We fractionated the postsynaptic densities to illustrate the differential distribution of p85S6K and p70S6K. Coimmunoprecipitation was performed to unveil interactions between p85S6K and the GluA1 subunit of AMPA receptor. The roles of p85S6K in synaptic targeting of GluA1 and learning and memory were evaluated by specific knockdown or overexpression of p85S6K followed by a broad range of methodologies including immunofluorescence, Western blot, in situ proximity ligation assay, morphological staining and behavioral examination. Further, the expression level of p85S6K was measured in brains from AD patients and AD model mice. Results p85S6K, but not p70S6K, was enriched in the postsynaptic densities. Moreover, knockdown of p85S6K resulted in defective spatial and recognition memory. In addition, p85S6K could interact with the GluA1 subunit of AMPA receptor through synapse-associated protein 97 and A-kinase anchoring protein 79/150. Mechanistic studies demonstrated that p85S6K could directly phosphorylate GluA1 at Ser845 and increase the amount of GluA1 in synapses, thus sustaining synaptic function and spine densities. Moreover, p85S6K was found to be specifically decreased in the synaptosomal compartment in the brains of AD patients and AD mice. Overexpression of p85S6K ameliorated the synaptic deficits and cognitive impairment in transgenic AD model mice. Conclusions These results strongly imply a significant role for p85S6K in maintaining synaptic and cognitive function by interacting with GluA1. The findings provide an insight into the rational targeting of p85S6K as a therapeutic potential for AD.

Ensembles of fear and extinction memories compete and interact to drive opposing behaviors. Here the authors identified insular cortical circuits as an executive gateway that decipher between fear and extinction memories via distinct subcortical pathways.

Abstract Background To generate high-quality bone scan SPECT images from only 1/7 scan time SPECT images using deep learning-based enhancement method. Materials and methods Normal-dose (925–1110 MBq) clinical technetium 99 m-methyl diphosphonate (99mTc-MDP) SPECT/CT images and corresponding SPECT/CT images with 1/7 scan time from 20 adult patients with bone disease and a phantom were collected to develop a lesion-attention weighted U2-Net (Qin et al. in Pattern Recognit 106:107404, 2020), which produces high-quality SPECT images from fast SPECT/CT images. The quality of synthesized SPECT images from different deep learning models was compared using PSNR and SSIM. Clinic evaluation on 5-point Likert scale (5 = excellent) was performed by two experienced nuclear physicians. Average score and Wilcoxon test were constructed to assess the image quality of 1/7 SPECT, DL-enhanced SPECT and the standard SPECT. SUVmax, SUVmean, SSIM and PSNR from each detectable sphere filled with imaging agent were measured and compared for different images. Results U2-Net-based model reached the best PSNR (40.8) and SSIM (0.788) performance compared with other advanced deep learning methods. The clinic evaluation showed the quality of the synthesized SPECT images is much higher than that of fast SPECT images (P 0.999), similar detail of 99mTc-MDP (P = 0.125) and the same diagnostic confidence (P = 0.1875). 4, 5 and 6 spheres could be distinguished on 1/7 SPECT, DL-enhanced SPECT and the standard SPECT, respectively. The DL-enhanced phantom image outperformed 1/7 SPECT in SUVmax, SUVmean, SSIM and PSNR in quantitative assessment. Conclusions Our proposed method can yield significant image quality improvement in the noise level, details of anatomical structure and SUV accuracy, which enabled applications of ultra fast SPECT bone imaging in real clinic settings.

Purpose: This study aims to evaluate the clinical performance of a deep learning (DL)‐enhanced two‐fold accelerated PET imaging method in patients with lymphoma. Methods: A total of 123 cases devoid of lymphoma underwent whole‐body 18F‐FDG‐PET/CT scans to facilitate the development of an advanced SAU2Net model, which combines the advantages of U2Net and attention mechanism. This model integrated inputs from simulated 1/2‐dose (0.07 mCi/kg) PET acquisition across multiple slices to generate an estimated standard dose (0.14 mCi/kg) PET scan. Additional 39 cases with confirmed lymphoma pathology were utilized to evaluate the model's clinical performance. Assessment criteria encompassed peak‐signal‐to‐noise ratio (PSNR), structural similarity index (SSIM), a 5‐point Likert scale rated by two experienced physicians, SUV features, image noise in the liver, and contrast‐to‐noise ratio (CNR). Diagnostic outcomes, including lesion numbers and Deauville score, were also compared. Results: Images enhanced by the proposed DL method exhibited superior image quality (P < 0.001) in comparison to low‐dose acquisition. Moreover, they illustrated equivalent image quality in terms of subjective image analysis and lesion maximum standardized uptake value (SUVmax) as compared to the standard acquisition method. A linear regression model with y = 1.017x + 0.110 (R2=1.00${R^2} = \;1.00$) can be established between the enhanced scans and the standard acquisition for lesion SUVmax. With enhancement, increased signal‐to‐noise ratio (SNR), CNR, and reduced image noise were observed, surpassing those of the standard acquisition. DL‐enhanced PET images got diagnostic results essentially equavalent to standard PET images according to two experienced readers. Conclusion: The proposed DL method could facilitate a 50% reduction in PET imaging duration for lymphoma patients, while concurrently preserving image quality and diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background: The application of deep learning methods in rapid bone scintigraphy is increasingly promising for minimizing the duration of SPECT examinations. Recent works showed several deep learning models based on simulated data for the synthesis of high‐count bone scintigraphy images from low‐count counterparts. Few studies have been conducted and validated on real clinical pairs due to the misalignment inherent in multiple scan procedures. Purpose: To generate high quality whole‐body bone images from 2× and 3× fast scans using deep learning based enhancement method. Materials and Methods: Seventy‐six cases who underwent whole‐body bone scans were enrolled in this prospective study. All patients went through a standard scan at a speed of 20 cm/min, which followed by fast scans consisting of 2× and 3× accelerations at speeds of 40 and 60 cm/min. A content‐attention image restoration approach based on Residual‐in‐Residual Dense Block (RRDB) is introduced to effectively recover high‐quality images from fast scans with fine‐details and less noise. Our approach is robust with misalignment introduced from patient's metabolism, and shows valid count‐level consistency. Learned Perceptual Image Patch Similarity (LPIPS) and Fréchet Inception Distance (FID) are employed in evaluating the similarity to the standard bone images. To further prove our method practical in clinical settings, image quality of the anonymous images was evaluated by two experienced nuclear physicians on a 5‐point Likert scale (5 = excellent). Results: The proposed method reaches the state‐of‐the‐art performance on FID and LPIPS with 0.583 and 0.176 for 2× fast scans and 0.583 and 0.185 for 3× fast scans. Clinic evaluation further demonstrated the restored images had a significant improvement compared to fast scan in image quality, technetium 99m‐methyl diphosphonate (Tc‐99 m MDP) distribution, artifacts, and diagnostic confidence. Conclusions: Our method was validated for accelerating whole‐body bone scans by introducing real clinical data. Confirmed by nuclear medicine physicians, the proposed method can effectively enhance image diagnostic value, demonstrating potential for efficient high‐quality fast bone imaging in practical settings. [ABSTRACT FROM AUTHOR]

Behavioral changes or neuropsychiatric symptoms (NPSs) are common features in dementia and are associated with accelerated cognitive impairment and earlier deaths. However, how NPSs are intertwined with cognitive decline remains elusive. In this study, we identify that the basolateral amygdala (BLA) is a key brain region that is associated with mood disorders and memory decline in the AD course. During the process from pre‐ to post‐onset in AD, the dysfunction of parvalbumin (PV) interneurons and pyramidal neurons in the amygdala leads to hyperactivity of pyramidal neurons in the basal state and insensitivity to external stimuli. We further demonstrate that serotonin (5‐HT) receptors in distinct neurons synergistically regulate the BLA microcircuit of AD rather than 5‐HT levels, in which both restrained inhibitory inputs by excessive 5‐HT1AR signaling in PV interneurons and depolarized pyramidal neurons via upregulated 5‐HT2AR contribute to aberrant neuronal hyperactivity. Downregulation of these two 5‐HT receptors simultaneously enables neurons to resist β‐amyloid peptides (Aβ) neurotoxicity and ameliorates the mood and cognitive defects. Therefore, our study reveals a crucial role of 5‐HT receptors for regulating neuronal homeostasis in AD pathogenesis, and this would provide early intervention and potential targets for AD cognitive decline. [ABSTRACT FROM AUTHOR]

In this article, we expound the important role of an emergency rescue system in handling public health emergencies, summarize the characteristics of China’s fight against the COVID-19 epidemic from the perspective of emergency rescue capacity building, and reflect on the experiences and lessons regarding emergency rescue to combat the epidemic. This study is expected to help improve relevant national policies and systems, strengthen the health protection net for the people, and maintain a sound environment for national security development in China. Moreover, we summarize the main contents and characteristics of the three stages for developing China’s emergency rescue system and analyze the existing problems from three aspects: mechanism, resources, and overall level. Furthermore, we propose several specific countermeasures and suggestions for the construction of the emergency rescue system for public health emergencies in China from the aspects of handling modes, scientific layout and function promotion, talent team construction, emergency material support, grass-roots capacity building, multi-disciplinary integration, scientific research–disease control–clinical treatment coordination, wartime mobilization mechanism, international cooperation, and action outline formulation.

Abstract The epigenetic clock is defined by the DNA methylation (DNAm) level and has been extensively applied to distinguish biological age from chronological age. Aging-related neurodegeneration is associated with epigenetic alteration, which determines the status of diseases. In recent years, extensive research has shown that physical exercise (PE) can affect the DNAm level, implying a reversal of the epigenetic clock in neurodegeneration. PE also regulates brain plasticity, neuroinflammation, and molecular signaling cascades associated with epigenetics. This review summarizes the effects of PE on neurodegenerative diseases via both general and disease-specific DNAm mechanisms, and discusses epigenetic modifications that alleviate the pathological symptoms of these diseases. This may lead to probing of the underpinnings of neurodegenerative disorders and provide valuable therapeutic references for cognitive and motor dysfunction.

Original citation: J Clin Invest. 2022;132(8):e149160. https://doi.org/10.1172/JCI149160. https://doi.org/10.1172/JCI168441 The left panel of Figure 5G originally showed a histogram that was inadvertently duplicated from Figure 5E. The correct figure panel is [...]

One aim of this study is to use non-Gaussian diffusion kurtosis imaging (DKI) for capturing microstructural abnormalities in gray matter of Alzheimer's disease (AD). The other aim is to compare DKI metrics against thickness of cortical gray matter and volume of deep gray matter, respectively. A cohort of 18 patients with AD, 18 patients with amnestic mild cognitive impairment (MCI), and 18 normal controls underwent morphological and DKI MR imaging. Images were investigated using regions-of-interest-based analyses for deep gray matter and vertex-wise analyses for cortical gray matter. In deep gray matter, more regions showed DKI parametric abnormalities than atrophies at the early MCI stage. Mean kurtosis (MK) exhibited the largest number of significant abnormalities among all DKI metrics. At the later AD stage, diffusional abnormalities were observed in fewer regions than atrophies. In cortical gray matter, abnormalities in thickness were mainly in the medial and lateral temporal lobes, which fit the locations of known early pathological changes. Microstructural abnormalities were predominantly in the parietal and even frontal lobes, which fit the locations of known late pathological changes. In conclusion, MK can complement conventional diffusion metrics for detecting microstructural changes, especially in deep gray matter. This study also provides evidence supporting the notion that microstructural changes predate morphological changes. Hum Brain Mapp 38:2495-2508, 2017. © 2017 Wiley Periodicals, Inc.

Ribulose‐1,5‐bisphosphate carboxylase/oxygenase (RuBisCO) is the enzyme responsible for the first step of carbon dioxide (CO2) fixation in plants, which proceeds via the carboxylation of ribulose 1,5‐biphosphate. Because of the enormous importance of this reaction in agriculture and the environment, there is considerable interest in the mechanism of fixation of CO2 by RuBisCO. Here, a serial synchrotron crystallography structure of spinach RuBisCO is reported at 2.3 Å resolution. This structure is consistent with earlier single‐crystal X‐ray structures of this enzyme and the results are a good starting point for a further push towards time‐resolved serial synchrotron crystallography in order to better understand the mechanism of the reaction. [ABSTRACT FROM AUTHOR]

Abstract Deficits in synaptic transmission and plasticity are thought to contribute to the pathophysiology of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Several brain stimulation techniques are currently available to assess or modulate human neuroplasticity, which could offer clinically useful interventions as well as quantitative diagnostic and prognostic biomarkers. In this review, we discuss several brain stimulation techniques, with a special emphasis on transcranial magnetic stimulation and deep brain stimulation (DBS), and review the results of clinical studies that applied these techniques to examine or modulate impaired neuroplasticity at the local and network levels in patients with AD or PD. The impaired neuroplasticity can be detected in patients at the earlier and later stages of both neurodegenerative diseases. However, current brain stimulation techniques, with a notable exception of DBS for PD treatment, cannot serve as adequate clinical tools to assist in the diagnosis, treatment, or prognosis of individual patients with AD or PD. Targeting the impaired neuroplasticity with improved brain stimulation techniques could offer a powerful novel approach for the treatment of AD and PD.

Postsynaptic structure assembly and remodeling are crucial for functional synapse formation during the establishment of neural circuits. However, how the specific scaffold proteins regulate this process during the development of the postnatal period is poorly understood. In this study, we find that the deficiency of ligand of Numb protein X 1 (Lnx1) leads to abnormal development of dendritic spines to impair functional synaptic formation. We further demonstrate that loss of Lnx1 promotes the internalization of EphB receptors from the cell surface. Constitutively active EphB2 intracellular signaling rescues synaptogenesis in Lnx1 mutant mice. Our data thus reveal a molecular mechanism whereby the Lnx1-EphB complex controls postsynaptic structure for synapse maturation during the adolescent period.

Mushroom spine loss and calcium dyshomeostasis are early hallmark events of age-related neurodegeneration, such as Alzheimer’s disease (AD), that are connected with neuronal hyperactivity in early pathology of cognitive brain areas. However, it remains elusive how these key events are triggered at the molecular level for the neuronal abnormality that occurs at the initial stage of disease. Here, we identify downregulated miR-339-5p and its upregulated target protein, neuronatin (Nnat), in cortex neurons from the presenilin-1 M146V knockin (PSEN1-M146V KI) mouse model of familial AD (FAD). Inhibition of miR-339-5p or overexpression of Nnat recapitulates spine loss and endoplasmic reticulum calcium overload in cortical neurons with the PSEN1 mutation. Conversely, either overexpression of miR-339-5p or knockdown of Nnat restores spine morphogenesis and calcium homeostasis. We used fiber photometry recording during the object-cognitive process to further demonstrate that the PSEN1 mutant causes defective habituation in neuronal reaction in the retrosplenial cortex and that this can be rescued by restoring the miR-339-5p/Nnat pathway. Our findings thus reveal crucial roles of the miR-339-5p/Nnat pathway in FAD that may serve as potential diagnostic and therapeutic targets for early pathogenesis.

Abstract Background Neuropsychiatric symptoms (NPS) such as depression, anxiety, apathy, and irritability occur in prodromal phases of clinical Alzheimer’s disease (AD), which might be an increased risk for later developing AD. Here we treated young APP/PS1 AD model mice prophylactically with serotonin-selective re-uptake inhibitor (SSRI) paroxetine and investigated the protective role of anti-depressant agent in emotional abnormalities and cognitive defects during disease progress. Methods To investigate the protective role of paroxetine in emotional abnormalities and cognitive defects during disease progress, we performed emotional behaviors of 3 months old APP/PS1 mouse following oral administration of paroxetine prophylactically starting at 1 month of age. Next, we tested the cognitive, biochemical and pathological, effects of long term administration of paroxetine at 6 months old. Results Our results showed that AD mice displayed emotional dysfunction in the early stage. Prophylactic administration of paroxetine ameliorated the initial emotional abnormalities and preserved the eventual memory function in AD mice. Conclusion Our data indicate that prophylactic administration of paroxetine ameliorates the emotional dysfunction and memory deficit in AD mice. These neuroprotective effects are attributable to functional restoration of glutamate receptor (GluN2A) in AD mice.

Purpose: A method named DECOMPOSE-QSM is developed to decompose bulk susceptibility measured with QSM into sub-voxel paramagnetic and diamagnetic components based on a three-pool complex signal model. Methods: Multi-echo gradient echo signal is modeled as a summation of three weighted exponentials corresponding to three types of susceptibility sources: reference susceptibility, diamagnetic and paramagnetic susceptibility relative to the reference. Paramagnetic component susceptibility (PCS) and diamagnetic component susceptibility (DCS) maps are constructed to represent the sub-voxel compartments by solving for linear and nonlinear parameters in the model. Results: Numerical forward simulation and phantom validation confirmed the ability of DECOMPOSE-QSM to separate the mixture of paramagnetic and diamagnetic components. The PCS obtained from temperature-variant brainstem imaging follows the Curie's Law, which further validated the model and the solver. Initial in vivo investigation of human brain images showed the ability to extract sub-voxel PCS and DCS sources that produce visually enhanced contrast between brain structures comparing to threshold QSM.

Quantitative susceptibility mapping (QSM) is a recently developed MRI technique for quantifying the spatial distribution of magnetic susceptibility within biological tissues. It first uses the frequency shift in the MRI signal to map the magnetic field profile within the tissue. The resulting field map is then used to determine the spatial distribution of the underlying magnetic susceptibility by solving an inverse problem. The solution is achieved by deconvolving the field map with a dipole field, under the assumption that the magnetic field is a result of the superposition of the dipole fields generated by all voxels and that each voxel has its unique magnetic susceptibility. QSM provides improved contrast to noise ratio for certain tissues and structures compared to its magnitude counterpart. More importantly, magnetic susceptibility is a direct reflection of the molecular composition and cellular architecture of the tissue. Consequently, by quantifying magnetic susceptibility, QSM is becoming a quantitative imaging approach for characterizing normal and pathological tissue properties. This article reviews the mechanism generating susceptibility contrast within tissues and some associated applications.

Quantitative susceptibility mapping (QSM) is a recently developed MRI technique for quantifying the spatial distribution of magnetic susceptibility within biological tissues. It first uses the frequency shift in the MRI signal to map the magnetic field profile within the tissue. The resulting field map is then used to determine the spatial distribution of the underlying magnetic susceptibility by solving an inverse problem. The solution is achieved by deconvolving the field map with a dipole field, under the assumption that the magnetic field is a result of the superposition of the dipole fields generated by all voxels and that each voxel has its unique magnetic susceptibility. QSM provides improved contrast to noise ratio for certain tissues and structures compared to its magnitude counterpart. More importantly, magnetic susceptibility is a direct reflection of the molecular composition and cellular architecture of the tissue. Consequently, by quantifying magnetic susceptibility, QSM is becoming a quantitative imaging approach for characterizing normal and pathological tissue properties. This article reviews the mechanism generating susceptibility contrast within tissues and some associated applications.

Objectives: To probe microstructural changes that are associated with subconcussive head impact exposure in deep and cortical gray matter of high school football players over a single season. Methods: Players underwent diffusion kurtosis imaging (DKI) and quantitative susceptibility mapping (QSM) scans. Head impact data was recorded. Association between parametric changes and frequency of frontal head impact was assessed. Results: In deep gray matter, significant decreases in mean kurtosis (MK) and increases in mean diffusivity (MD) over the season were observed in the thalamus and putamen. Correlations between changes in DKI metrics and frequency of frontal impacts were observed in the putamen and caudate.In cortical gray matter, decreases in MK were observed in regions including the pars triangularis and inferior parietal. In addition, increases in MD were observed in the rostral middle frontal cortices. Negative correlations between MK and frequency of frontal impacts were observed in the posterior part of the brain including the pericalcarine, lingual and middle temporal cortices.Magnetic susceptibility values exhibited no significant difference or correlation, suggesting these diffusion changes common within the group may not be associated with iron-related mechanisms. Conclusion: Microstructural alterations over the season and correlations with head impacts were captured by DKI metrics, which suggested that DKI imaging of gray matter may yield valuable biomarkers for evaluating brain injuries associated with subconcussive head impact. Findings of associations between frontal impacts and changes in posterior cortical gray matter also indicated that contrecoup injury rather than coup injury might be the dominant mechanism underlying the observed microstructural alterations. Advances in knowledge: Significant microstructural changes, as reflected by DKI metrics, in cortical gray matter such as the rostral middle frontal cortices, and in deep gray matter such as the thalamus were observed in high school football players over the course of a single season without clinically diagnosed concussion.QSM showed no evidence of iron-related changes in the observed subconcussive brain injuries.The detected microstructural changes in cortical and deep gray matter correlated with frequency of subconcussive head impacts. Implications for patient care: DKI may yield valuable biomarkers for evaluating the severity of brain injuries associated with subconcussive head impacts in contact sport athletes.

Mushroom spine loss and calcium dyshomeostasis are early hallmark events of age-related neurodegeneration, such as Alzheimer's disease (AD), that are connected with neuronal hyperactivity in early pathology of cognitive brain areas. However, it remains elusive how these key events are triggered at the molecular level for the neuronal abnormality that occurs at the initial stage of disease. Here, we identify downregulated miR-339-5p and its upregulated target protein, neuronatin (Nnat), in cortex neurons from the presenilin-1 M146V knockin (PSEN1-M146VKI) mouse model of familial AD (FAD). Inhibition of miR-339-5p or overexpression of Nnat recapitulates spine loss and endoplasmic reticulum calcium overload in cortical neurons with the PSEN1 mutation. Conversely, either overexpression of miR-339-5p or knockdown of Nnat restores spine morphogenesis and calcium homeostasis. We used fiber photometry recording during the object-cognitive process to further demonstrate that the PSEN1 mutant causes defective habituation in neuronal reaction in the retrosplenial cortex and that this can be rescued by restoring the miR-339-5p/Nnat pathway. Our findings thus reveal crucial roles of the miR-339-5p/Nnat pathway in FAD that may serve as potential diagnostic and therapeutic targets for early pathogenesis., Introduction Alzheimer's disease (AD) is one of the most prevalent age-related neurodegenerative disorders and is characterized by progressive memory impairment and cognitive deficits, often manifested pathologically by the deposition of [...]

ObjectiveTo improve the assessment of primary tumor heterogeneity in magnetic resonance imaging (MRI) of non-small cell lung cancer (NSCLC), we proposed a method using basic measurements from T1- and T2-weighted MRI.MethodsOne hundred and four NSCLC patients with different T stages were studied. Fifty-two patients were analyzed as training group and another 52 as testing group. The ratios of standard deviation (SD)/mean signal value of primary tumor from T1-weighted (T1WI), T1-enhanced (T1C), T2-weighted (T2WI), and T2 fat suppression (T2fs) images were calculated. In the training group, correlation analyses were performed between the ratios and T stages. Then an ordinal regression model was built to generate the tumor heterogeneous index (THI) for evaluating the heterogeneity of tumor. The model was validated in the testing group.ResultsThere were 11, 32, 40, and 21 patients with T1, T2, T3, and T4 disease, respectively. In the training group, the median SD/mean on T1WI, T1C, T2WI, and T2fs sequences was 0.11, 0.19, 0.16, and 0.15 respectively. The SD/mean on T1C (p=0.003), T2WI (p=0.000), and T2fs sequences (p=0.002) correlated significantly with T stages. Patients with more advanced T stage showed higher SD/mean on T2-weighted, T2fs, and T1C sequences. The median THI in the training group was 2.15. THI correlated with T stage significantly (p=0.000). In the testing group, THI was also significantly related to T stages (p=0.001). Higher THI had relevance to more advanced T stage.ConclusionsThe proposed ratio measurements and THI based on MRI can serve as functional radiomic markers that correlated with T stages for evaluating heterogeneity of lung tumors.