Plaque Location Research Articles

Refining the amyloid β peptide and oligomer fingerprint ambiguities in Alzheimer's disease: Mass spectrometric molecular characterization in brain, cerebrospinal fluid, blood, and plasma.

Since its discovery, amyloid-β (Aβ) has been the principal target of investigation of in Alzheimer's disease (AD). Over the years however, no clear correlation was found between the Aβ plaque burden and location, and AD-associated neurodegeneration and cognitive decline. Instead, diagnostic potential of specific Aβ peptides and/or their ratio, was established. For instance, a selective reduction in the concentration of the aggregation-prone 42 amino acid-long Aβ peptide (Aβ42) in cerebrospinal fluid (CSF) was put forward as reflective of Aβ peptide aggregation in the brain. With time, Aβ oligomers-the proposed toxic Aβ intermediates-have emerged as potential drivers of synaptic dysfunction and neurodegeneration in the disease process. Oligomers are commonly agreed upon to come in different shapes and sizes, and are very poorly characterized when it comes to their composition and their "toxic" properties. The concept of structural polymorphism-a diversity in conformational organization of amyloid aggregates-that depends on the Aβ peptide backbone, makes the characterization of Aβ aggregates and their role in AD progression challenging. In this review, we revisit the history of Aβ discovery and initial characterization and highlight the crucial role mass spectrometry (MS) has played in this process. We critically review the common knowledge gaps in the molecular identity of the Aβ peptide, and how MS is aiding the characterization of higher order Aβ assemblies. Finally, we go on to present recent advances in MS approaches for characterization of Aβ as single peptides and oligomers, and convey our optimism, as to how MS holds a promise for paving the way for progress toward a more comprehensive understanding of Aβ in AD research.

Prognostic Significance Of Plaque Location In Non-obstructive Coronary Artery Disease: From The Confirm Registry

Introduction: Obstructive coronary artery disease (CAD) in proximal coronary segments is associated with a poor prognosis. However, the contribution of proximal plaque location to major adverse cardiovascular events (MACE) among patients with nonobstructive CAD is not well defined. We examined MACE risk in relation to the location of non-obstructive coronary artery plaque by coronary CT angiography (CCTA).

Plaque Location And Vessel Geometry On Coronary Computed Tomography Angiography Predict Future Culprit Lesions Associated With Acute Coronary Syndrome: Results From The ICONIC Study

Introduction: Coronary computed tomography angiography (CCTA) enables three-dimensional reconstruction of the coronary tree and hence precise assessment of plaque distribution and vessel geometric features. We evaluated if CCTA-derived geometric lesion characteristics (GLCs) encompassing plaque location and vessel geometry add to stenosis severity and morphological plaque assessment for predicting future culprit lesions associated with acute coronary syndrome (ACS).

Prevalence of Dermoscopic signs in Egyptian psoriatic patients with different skin phototypes and different plaque locations

Dermoscopy is a non-invasive technique that has been recently utilized for the diagnosis and management of many skin disorders. It also provides information about inflammatory skin diseases e.g. psoriasis, lupus, and so on. Psoriasis is a papulosquamous disease with variable distribution, morphology, severity and course, affecting about 1.5% of the population. In this study 218 cases of classic psoriasis were examined clinically and by dermoscopy. Dermoscopic signs found in psoriasis were bushy capillaries (dotted vessels), erythema and scales. Bushy capillaries presented in 99.5% of all cases, erythema presented also in 99.5% and scales presented in 92.7%. We found that, type and site of psoriasis have little or no effect on erythema but have significant effect on scales especially flexural psoriasis due to humidity, and skin phototype has no or little effect on dermoscopic finding in psoriasis as there is no significant effect of skin color on visibility of the bushy capillaries, erythema or scales. In conclusion, the well-known dermoscopic criteria of psoriasis, namely bushy capillaries, erythema and scaling are seen in dark skin as well as in those in light skin, in lesions of different locations, with the frequency of white scales varying among different body sites.

Effects of the Haemodynamic Stimulus on the Location of Carotid Plaques Based on a Patient-Specific Mechanobiological Plaque Atheroma Formation Model.

In this work, we propose a mechanobiological atheroma growth model modulated by a new haemodynamic stimulus. To test this model, we analyse the development of atheroma plaques in patient-specific bifurcations of carotid arteries for a total time of 30 years. In particular, eight geometries (left or right carotid arteries) were segmented from clinical images and compared with the solutions obtained computationally to validate the model. The influence of some haemodynamical stimuli on the location and size of plaques is also studied. Plaques predicted by the mechanobiological models using the time average wall shear stress (TAWSS), the oscillatory shear index (OSI) and a new index proposed in this work are compared. The new index predicts the shape index of the endothelial cells as a combination of TAWSS and OSI values and was fitted using data from the literature. The mechanobiological model represents an evolution of the one previously proposed by the authors. This model uses Navier-Stokes equations to simulate blood flow along the lumen in the transient mode. It also employs Darcy's law and Kedem-Katchalsky equations for plasma and substance flow across the endothelium using the three-pore model. The mass balances of all the substances that have been considered in the model are implemented by convection-diffusion-reaction equations, and finally the growth of the plaques has been computed. The results show that by using the new mechanical stimulus proposed in this study, prediction of plaques is, in most cases, better than only using TAWSS or OSI with a minimal and maximal errors on stenosis ratio of 2.77 and 32.89 %, respectively. However, there are a few geometries in which haemodynamics cannot predict the location of plaques, and other biological or genetic factors would be more relevant than haemodynamics. In particular, the model predicts correctly eleven of the fourteen plaques presented in all the geometries considered. Additionally, a healthy geometry has been computed to check that plaque is not developed with the model in this case.

Site-specific Phenotype of Atherosclerotic Lesions According to Their Location Within the Coronary Tree – a CCTA-based Study of Vulnerable Plaques

Abstract Background: The evaluation of site-specific phenotype according to the topographic location of atherosclerotic lesions within the coronary tree has not been studied so far. The present study is based on the premise that the location of coronary plaques can influence their composition and degree of vulnerability. Aim: To evaluate different phenotypes of vulnerable coronary plaques across the three major coronary arteries in terms of composition, morphology, and degree of vulnerability, in patients with chest pain and low-to-intermediate probability of coronary artery disease, using coronary computed tomography angiography (CCTA) and a complex plaque analysis. Material and methods: This was a cross-sectional study on 75 subjects undergoing CCTA for chest pain, who presented at least one vulnerable coronary plaque (VP), defined as the presence of ≥1 CT vulnerability marker (low attenuation plaque, napkin-ring sign, spotty calcifications, positive remodeling). The study included per plaque analysis of 90 vulnerable coronary lesions identified in various locations within the coronary tree as follows: n = 30 VPs in the left anterior descending artery (LAD), n = 30 VPs in the circumflex artery (CXA), and n = 30 VPs in the right coronary artery (RCA). Results: The RCA exhibited significantly longer VPs (p = 0.001), with the largest volume (p = 0.0007) compared to those arising from the LAD and CXA. Vulnerable plaques located in the LAD exhibited a significantly more calcified phenotype (calcified volume: LAD – 44.07 ± 63.90 mm3 vs. CXA – 12.40 ± 19.65 mm3 vs. RCA – 33.69 ± 34.38 mm3, p = 0.002). Plaques from the RCA presented a more non-calcified phenotype, with the largest non-calcified (p = 0.002), lipid rich (p = 0.0005), and fibrotic volumes (p = 0.003). Low-attenuation plaques were most frequent in the RCA (p = 0.0009), while the highest vulnerability degree was present in lesions located in the LAD, which presented the highest number of vulnerability markers per plaque (p = 0.01). Conclusions: Vulnerable plaques arising from the right coronary artery are longer, more vo-luminous and with larger lipid and non-calcified content, whereas those located in the left anterior descending artery present a higher volume of calcium, but also a higher degree of vulnerability. The least vulnerable lesions were present in the circumflex artery.

Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice-From Bench to Bedside.

In the 1900s, researchers established animal models experimentally to induce atherosclerosis by feeding them with a cholesterol-rich diet. It is now accepted that high circulating cholesterol is one of the main causes of atherosclerosis; however, plaque localization cannot be explained solely by hyperlipidemia. A tremendous amount of studies has demonstrated that hemodynamic forces modify endothelial athero-susceptibility phenotypes. Endothelial cells possess mechanosensors on the apical surface to detect a blood stream-induced force on the vessel wall, known as “wall shear stress (WSS)”, and induce cellular and molecular responses. Investigations to elucidate the mechanisms of this process are on-going: on the one hand, hemodynamics in complex vessel systems have been described in detail, owing to the recent progress in imaging and computational techniques. On the other hand, investigations using unique in vitro chamber systems with various flow applications have enhanced the understanding of WSS-induced changes in endothelial cell function and the involvement of the glycocalyx, the apical surface layer of endothelial cells, in this process. In the clinical setting, attempts have been made to measure WSS and/or glycocalyx degradation non-invasively, for the purpose of their diagnostic utilization. An increasing body of evidence shows that WSS, as well as serum glycocalyx components, can serve as a predicting factor for atherosclerosis development and, most importantly, for the rupture of plaques in patients with high risk of coronary heart disease.

Effect of Presence of Ramus Intermedius Artery on Location of Culprit Lesions in Acute Left Circumflex Coronary Artery Occlusion.

Background and aimCoronary artery anatomy frequently affects location of atherosclerotic plaques and subsequent culprit lesions. We sought to clarify whether presence or absence of Ramus Intermedius coronary artery (RI) would affect location of culprit lesions in acute left circumflex (LCX) coronary artery occlusion.MethodsThe study included 180 patients, 100 with a diagnosis of non-ST elevation myocardial infarction (NSTEMI) and 80 with ST elevation myocardial infarction (STEMI). All culprit lesions were located in the LCX coronary artery. RI group included 45 patients and the No RI group included 135 patients.ResultsCulprit LCX lesions were similarly located at a comparable distance from LCX ostium in both groups and the presence of RI was not associated with significantly more proximally located culprit LCX lesions (34.7 ± 15.2 mm compared to 30.8 ± 17.9 mm respectively, p > 0.05). The frequency distribution of culprit lesions’ distance from LCX ostium showed no significant difference between both groups in any of the segments studied (10 mm each). There was no significant difference between both groups regarding markers of myocardial necrosis size as cardiac biomarkers (peak cardiac troponin-T 1077.4 ± 361.2 pg/dl vs 926 ± 462.2 pg/dl respectively, p = 0.13), (peak creatine kinase-MB 232.2 ± 81 ng/dl vs 194.7 ± 99.2 ng/dl respectively, p = 0.07) or left ventricular ejection fraction (EF 46.3 ± 6.3% vs 48.3 ± 8.3% respectively, p = 0.76).ConclusionPresence of RI coronary artery, as an additional flow divider, may not be associated with more proximal culprit lesions, compared to its absence, in cases of acute LCX coronary artery occlusion. Possible underlying pathophysiologic mechanisms remain to be clarified.

Multimodal, label-free fluorescence and Raman imaging of amyloid deposits in snap-frozen Alzheimer\u2019s disease human brain tissue

Alzheimer’s disease (AD) neuropathology is characterized by hyperphosphorylated tau containing neurofibrillary tangles and amyloid-beta (Aβ) plaques. Normally these hallmarks are studied by (immuno-) histological techniques requiring chemical pretreatment and indirect labelling. Label-free imaging enables one to visualize normal tissue and pathology in its native form. Therefore, these techniques could contribute to a better understanding of the disease. Here, we present a comprehensive study of high-resolution fluorescence imaging (before and after staining) and spectroscopic modalities (Raman mapping under pre-resonance conditions and stimulated Raman scattering (SRS)) of amyloid deposits in snap-frozen AD human brain tissue. We performed fluorescence and spectroscopic imaging and subsequent thioflavin-S staining of the same tissue slices to provide direct confirmation of plaque location and correlation of spectroscopic biomarkers with plaque morphology; differences were observed between cored and fibrillar plaques. The SRS results showed a protein peak shift towards the β-sheet structure in cored amyloid deposits. In the Raman maps recorded with 532 nm excitation we identified the presence of carotenoids as a unique marker to differentiate between a cored amyloid plaque area versus a non-plaque area without prior knowledge of their location. The observed presence of carotenoids suggests a distinct neuroinflammatory response to misfolded protein accumulations.

The Longitudinal Distribution and Stability of Curved Basilar Artery Plaque: A Study Based on HR-MRI.

Aims: This study aims to evaluate the differences in the characteristics of atherosclerotic plaques in the proximal, curved, and distal segments of the curved basilar artery (BA) through high-resolution magnetic resonance imaging(HR-MRI). Methods: The imaging and clinical data of 146 patients were retrospectively analyzed. On the basis of three-dimensional (3D) time -of -flight magnetic resonance angiography (3D-TOF-MRA), 51 patients with BA curvature were selected for the study. The BA plaque is divided into three groups: proximal, curved, and distal. Plaques were identified and analyzed according to spin echo acquisition imaging via T1-weighted 3D volumetric isotropic Tse acquisition (T1W-3D -VISTA), and compare the differences in clinical related factors and plaque characteristics between groups. Diffusion-weighted imaging (DWI) and/or T2WI identified brainstem infarction. The patients were divided into symptomatic and asymptomatic groups. The correlation between plaque location and symptoms was identified and analyzed. Results: Among 51 patients, a total of 376 plaques were detected. Plaques in the proximal and curved segments are more common than those in the distal segments. Proximal plaques are more likely to have intraplaque hemorrhage ( P =0.002 ＜0.05). There was no significant difference in the distribution of criminal plaques and non-criminal plaques between each group ( P =0.36 ＞0.05). Conclusion: Plaques in the proximal and curved segments of the BA are more common than those in the distal segments. The proximal plaque is more prone to intraplaque hemorrhage.

Contribution of atherosclerotic plaque location and severity to the near-wall hemodynamics of the carotid bifurcation: an experimental study and FSI modeling.

Atherosclerosis is initiated by endothelial injury that is related to abnormal values of hemodynamic parameters such as wall shear stress (WSS), oscillatory shear index (OSI) and stress phase angle (SPA), which are more common in arterial bifurcations due to the complex structure. An experimental model of human carotid bifurcation with accurate geometrical and mechanical features was set up, and using realistic pulsatile flow rates, the inlet and outlet pressure pulses were measured for normal and stenosed models with 40% and 80% severities at common carotid (CCA), internal carotid (ICA) and external carotid (ECA) arteries. Based on the obtained experimental data, fluid-structure models were developed to obtain WSS, OSI, and SPA and evaluate pathological consequences at different locations. Mild severity had minor impact, however, inducing severe 80% stenosis in each branch led to considerable localized changes of hemodynamic parameters both in the stenosis site and other locations. This included sharp increases in WSS values accompanied by very low values close to zero before and after the peaks. Severe stenosis not only caused significant changes in the local artery, but also in other branches. OSI and SPA were less sensitive to stenosis, although high peaks were observed on bifurcation site for the stenosis at ECA. The interconnection of arteries at carotid bifurcation results in altered pressure/flow patterns in all branches when a stenosis is applied in any site. Such effect confirms pathological findings that atherosclerotic plaques are observed simultaneously in different carotid branches, although with different degrees of plaque growth and severity.

Characterisation of symptomatic intracranial plaque without substantial stenosis using high-resolution vessel wall MRI

To characterise symptomatic intracranial plaque without substantial stenosis using three-dimensional (3D) high-resolution contrast-enhanced black-blood magnetic resonance imaging (BBMRI) and to determine plaque features associated with recent cerebrovascular events. The institutional review board approved this retrospective study. The case notes from patients with evidence of intracranial atherosclerosis in a large intracranial artery with preceding BBMRI were reviewed retrospectively. Symptomatic and asymptomatic plaques with substantial luminal stenosis (<50%) were matched by plaque location and patient age. All MRI images were de-identified and interpreted by two neuroradiologists who were blinded to the history of symptoms. Qualitative analyses including the presence of intraplaque haemorrhage (IPH), eccentricity, surface irregularity, and grade of plaque enhancement were recorded. Quantitative analyses including normal wall index and degree of contrast enhancement were calculated. Multivariate regression analysis was performed to identify the association with cerebrovascular ischaemic events. A total of 38 pairs of symptomatic and asymptomatic plaques from 74 patients were analysed. Compared to asymptomatic plaques, symptomatic plaques demonstrated higher degree of contrast enhancement (29.77±19.23 versus 18.21±12.18%, p=0.039) and presence of IPH (26% versus 8%, p=0.032). No significant differences were detected regarding eccentricity, surface irregularity, and normal wall index. Events were associated with contrast enhancement (OR, 1.212; 95% confidence interval [CI], 1.086-1.352) after controlling for age, sex, cardiovascular risk factors, and stenosis degree. IPH was not associated with events. Contrast enhancement in the intracranial plaque without substantial stenosis is associated with previous events, and may serve as the vulnerable feature, thereby stratifying stroke risk not achievable by luminal stenosis.

Imaging coronary plaques using 3D motion-compensated [18F]NaF PET/MR

BackgroundCardiac PET has recently found novel applications in coronary atherosclerosis imaging using [18F]NaF as a radiotracer, highlighting vulnerable plaques. However, the resulting uptakes are relatively small, and cardiac motion and respiration-induced movement of the heart can impair the reconstructed images due to motion blurring and attenuation correction mismatches. This study aimed to apply an MR-based motion compensation framework to [18F]NaF data yielding high-resolution motion-compensated PET and MR images.MethodsFree-breathing 3-dimensional Dixon MR data were acquired, retrospectively binned into multiple respiratory and cardiac motion states, and split into fat and water fraction using a model-based reconstruction framework. From the dynamic MR reconstructions, both a non-rigid cardiorespiratory motion model and a motion-resolved attenuation map were generated and applied to the PET data to improve image quality. The approach was tested in 10 patients and focal tracer hotspots were evaluated concerning their target-to-background ratio, contrast-to-background ratio, and their diameter.ResultsMR-based motion models were successfully applied to compensate for physiological motion in both PET and MR. Target-to-background ratios of identified plaques improved by 7 ± 7%, contrast-to-background ratios by 26 ± 38%, and the plaque diameter decreased by −22 ± 18%. MR-based dynamic attenuation correction strongly reduced attenuation correction artefacts and was not affected by stent-related signal voids in the underlying MR reconstructions.ConclusionsThe MR-based motion correction framework presented here can improve the target-to-background, contrast-to-background, and width of focal tracer hotspots in the coronary system. The dynamic attenuation correction could effectively mitigate the risk of attenuation correction artefacts in the coronaries at the lung-soft tissue boundary. In combination, this could enable a more reproducible and reliable plaque localisation.

Familial hypercholesterolemia and vulnerability of coronary plaque in patients with coronary artery disease

ObjectivesPatients with familial hypercholesterolemia (FH) are at a very high risk of coronary artery diseases. The aim of the present study was to clarify the characteristics of coronary plaque in patients with FH. Designand Methods: A total of 569 patients who underwent optical coherence tomography (OCT) imaging of culprit plaque were included. The characteristics of culprit plaque were compared between patients with and without FH. ResultsA total of 38 patients (6.7%) were clinically diagnosed with FH. The location of the culprit plaque was significantly different (p ​< ​0.001) with a trend toward higher frequency of left main lesion in the FH group than in the group with no FH (7.9 vs. 0%). Culprit plaque was significantly shorter in patients with FH than those without FH (28.1 vs. 33.2 ​mm, p ​= ​0.016). A trend toward higher prevalence of plaque with macrophage accumulation in patients with FH than those without FH (50.0 vs. 34.7%, p ​= ​0.056) was observed, although the prevalence of other vulnerable characteristics including thin-cap fibroatheroma (TCFA) was comparable between patients with and without FH. Among patients with FH, significant increases in the prevalence of lipid-rich plaque (p ​= ​0.028) and TCFA (p ​= ​0.003) were observed according to the increase in low-density lipoprotein cholesterol (LDL-C) levels. ConclusionsPatients with FH had shorter culprit plaque without significant difference in the prevalence of vulnerable plaque components compared with patients without FH. A higher LDL-C level was associated with higher prevalence of vulnerable plaque in patients with FH.

Comparison of plaque characteristics of small and large subcortical infarctions in the middle cerebral artery territory using high-resolution magnetic resonance vessel wall imaging

The characteristics of plaque that ultimately lead to different subcortical infarctions remain unclear. We explored the differences in plaque characteristics between patients with small subcortical infarction (SSI) and large subcortical infarction (LSI) of the middle cerebral artery (MCA) using high-resolution magnetic resonance vessel wall imaging (HR-MRVWI). The study group comprised 71 patients (mean age, 47.49±11.5 years; 55 male) with MCA territory ischemic stroke. Whole-brain HR-MRVWI was performed using a three-dimensional T1-weighted variable-flip-angle turbo spin echo (SPACE) sequence. Patients were divided into SSI and LSI groups based on routine MRI images. Plaque distribution was classified as the superior, inferior, ventral, or dorsal wall of the MCA. The number of quadrants with plaque formation, location of plaque, plaque burden (PB), arterial remodeling pattern (positive or negative), and degree of stenosis were analyzed and compared between groups. Of the 71 patients, 43 (60.6%) and 28 (39.4%) were identified as the SSI and LSI groups, respectively. The proportion of plaques involving only one quadrant was significantly higher in the SSI group, and these plaques were located in the superior or dorsal MCA vessel wall. There was no significant difference between groups in the proportion of plaques involving two or more quadrants, plaque distribution, or PB. Most plaques in both groups showed positive remodeling, and the percentage of remodeling pattern was similar. A significantly higher incidence of low-grade stenosis (<50%) was observed in the SSI group. Both SSI and LSI may be associated with major intracranial artery atherosclerosis, but patients with SSI showed relatively fewer quadrants with plaque formation and a lesser degree of stenosis.

Intra-operative ocular ultrasonography of iodine-125 brachytherapy plaques in patients with uveal melanoma.

PurposeBrachytherapy with iodine-125 (125I) has been extensively used as a conservative treatment for uveal melanoma (UM). Surgical technique for correct placement of episcleral radioactive plaques (ERP) in UM cases with posterior choroidal location and/or small size can be difficult and inaccurate. In this study, the correct positioning of plaques was assessed by intra-operative ultrasound control.Material and methodsThis was a longitudinal, retrospective study of consecutive 20 patients with UM (small-medium size and/or posterior location) who received 125I brachytherapy. Location of plaques was adjusted by intra-operative ocular ultrasonography control. To perform ocular intra-operative ultrasonography, a 10 MHz probe was used to longitudinal and transverse bases in corresponding dummy plaques.ResultsThe study included 8 males and 12 females, with a mean age of 66.3 years (SD = 14.53), 5 right eyes (RE) and 15 left eyes (LE). In ultrasound examination, 4 UMs were of mushroom morphology and the rest nodular. Means of the size of UM by ultrasound were (mm): Lb: 10.60 (SD = 2.24) × Tb: 9.88 (SD = 1.54) × H: 4.02 (SD = 1.44) (3 cases corresponding to small size of collaborative ocular melanoma study (COMS), and 17 cases to medium). The plaques used were between 14 and 20 mm in diameter, with an average distance between the edge of greater base of the tumor and the edge of plate of 2.44 mm (SD = 0.34). It was necessary to surgically reposition the plaque in 4 cases (20%).ConclusionsIntra-operative ultrasound control improves the accuracy of radioactive plaque placement for the treatment of medium-small UMs in posterior location. Probably, this technique should be applied in all cases of brachytherapy, regardless of the isotope chosen and the location of tumor mass, in order to perfectly adjust therapeutic position.

Guiding catheter extension compatibility for high speed rotational atherectomy.

Coronary calcification is one of the features that characterize atherosclerosis. The location of a calcific plaque may vary from case to case [1]. Some distal locations may affect procedural outcomes of coronary angioplasty, resulting in impaired device deliverability. In these cases, guiding extension catheters have been widely introduced into practice to overcome the problem of poor deliverability and guiding catheter support. In some patients, calcified lesions are located distally and rotational burr deliverability is also impaired. The aim of this study was to test the commercially available guiding extension catheters in terms of compatibility of these devices with rotational atherectomy burrs outside the patient’s body.

Prospective Memory Deficits in Multiple Sclerosis: Voxel-based Morphometry and Double Inversion Recovery Analysis.

Objective Prospective memory (PM) is an important social cognitive function in everyday life. PM is one of the most affected cognitive domains in multiple sclerosis (MS) patients. Gray matter (GM) atrophy and plaques have been attracting attention for various cognitive impairments in MS patients. This study aimed to clarify the atrophic GM regions associated with PM deficits and investigate the relationship between the atrophic GM regions and GM plaques. Methods Twenty-one MS patients and 10 healthy controls (HCs) underwent neuropsychological tests and MRI. PM was assessed using subtests of the Rivermead Behavioural Memory Test. A lesion symptom analysis was performed using voxel-based morphometry (VBM). We then evaluated GM plaques in the corresponding areas using double inversion recovery (DIR). Results MS patients showed lower PM scores than HCs (p=0.0064). The GM volume of MS patients tended to be lower than those of HCs. VBM analyses revealed correlations of the PM score with the orbital part of the left inferior frontal gyrus, the left hippocampus, and the right parahippocampus. There was no GM plaque in the orbital part of the left inferior frontal gyrus and the right parahippocampus. Only one patient (4.8%) had GM plaque in the left hippocampus. Conclusion The left inferior frontal gyrus, the left hippocampus, and the right parahippocampus were associated with PM in MS, whereas these atrophic GM regions were not associated with GM plaque. Regardless of the location of plaques on DIR, both PM deficit and GM atrophy should be detected using neuropsychological tests and VBM in MS patients.

Evaluation of the morphological and clinical features of left anterior descending myocardial bridging with multi-detector computed tomography.

AimThe aim of the study was to assess the incidence, localization, depth, length of myocardial bridging (MB) with left anterior descending (LAD), systolic compression ratio, atherosclerotic plaque localization and degree of stenosis by 256-slice multi-detector computed tomography (MDCT).Material and methodsComputed tomography (CT) scans from a total of 3947 patients who underwent MDCT were reviewed retrospectively for LAD MB. A diastolic and systolic dataset with the best image quality was selected. Myocardial bridge was defined as a coronary artery with an intra-myocardial course. Myocardial bridging was divided into “deep” or “superficial”. The length and depth of the bridging segment were calculated. For each bridging segment, the presence of atherosclerosis was saved in a 2-cm-long segment proximal to the entry of the bridging segment. The degree of stenosis made by atherosclerotic plaques was determined.ResultsLAD myocardial bridging was detected in 410 (10.4%) patients. Among these, 97 (23.7%) patients had a deep and 313 (76.3%) patients had a superficial course. The mean LAD MB length was 20.28 ±9.63 mm and the depth was 1.72 ±1.11 mm. The systolic and diastolic mean diameter difference was 0.193 mm and the average compression ratio was 9.44%. Atherosclerotic plaques were found in 167 (40.7%) of 410 LAD MB. Atherosclerotic plaques were found in 50.5% of deep MB and 37.7% of superficial MB.Conclusions256-slice MDCT coronary angiography has a high sensitivity to show myocardial bridging in LAD localization, to determine length, depth, compression ratio, atherosclerotic plaque localization and degree of stenosis.

Translational potential of mouse CSF biomarkers in Alzheimer’s disease: Association of CSF neurogranin with tau, NFL and amyloid pathology in APP knock‐in mouse models

AbstractBackgroundAlzheimer’s disease (AD) is characterized by early and progressive synaptic dysfunction and loss that are closely related to cognitive impairment in AD patients. Neurogranin (Ng) has emerged as a potential marker of synaptic dysfunction, with cerebrospinal fluid (CSF) levels specifically increased in AD. In order to investigate the translational potential of CSF Ng, the present study investigated its alterations and relationship to AD‐related pathology (Aβ42, tau and neurofilament light; NFL) in both CSF and brain tissue of novel App knock‐in mouse models.MethodsCSF and brain tissue were sampled from 12‐months old wild type (WT), AppNL‐F/NL‐F and AppNL‐G‐F/NL‐G‐F mice. CSF and brain (cortex and hippocampus) Ng, Aβ42, t‐tau and NFL protein levels were analyzed using new ultra sensitive digital enzyme‐linked immunosorbent assays on the Simoa platform. Differences in expression of Ng in the brain tissue and its relation to amyloid plaques in App knock‐in mice were investigated by immunohistochemistry (IHC).ResultsCSF Ng, t‐tau and NFL levels were significantly increased in App knock‐in compared to WT mice (p &lt; 0.05). CSF Ng negatively correlated with Ng levels in the cortex and Aβ42 levels in the CSF and positively correlated with CSF t‐tau and NFL levels (p &lt; 0.05). Loss of neurogranin in the dendrites of hippocampal CA1 region of App knock‐in mice was closely associated with the localization of Aβ plaques in double IHC stainings.ConclusionsApp knock‐in mice exhibit synaptic degeneration that is associated with AD neuropathology and remarkably comparable to findings from clinical studies. CSF Ng is potential translational marker of synaptic degeneration in AD.