Plaque Distribution Research Articles

Association of Perforator Stroke After Basilar Artery Stenting With Negative Remodeling.

Background and Purpose- We try to evaluate whether plaque features and perforator stroke after intracranial stenting is associated with the arterial remodeling patterns in patients with severe basilar artery stenosis. Methods- We studied patients with symptomatic intracranial arterial stenosis who underwent high-resolution magnetic resonance imaging from September 2014 to January 2017. Among them, patients with basilar artery stenosis underwent angioplasty and stenting were recruited. Arterial remodeling patterns were divided into negative or nonnegative remodeling. Plaque features were investigated by high-resolution magnetic resonance imaging, which includes plaque distribution, intraplaque hemorrhage, calcification, as well as enhancement patterns. Incidence of perforator strokes after intracranial stenting was recorded. Plaque features and incidence of poststenting perforator stroke were compared between negative and nonnegative remodeling. Results- Two hundred ninety-eight consecutive patients were enrolled. Among them, 30 patients fulfilled the inclusion criteria. There were 11 patients (36.7%) with negative remodeling and 19 (63.3%) with nonnegative remodeling. Twenty-six patients (86.7%) had diffuse distribution, 5 patients (16.7%) had intraplaque hemorrhage, 2 patients (6.7%) had calcification, and 17 patients (65.4%) had enhancement. Three patients had perforator stroke after stenting. Plaque features were similar between negative and nonnegative remodeling groups. Patients with negative remodeling were more likely to have perforator stroke after stenting comparing with patients with nonnegative remodeling (27.3% versus 0%, P=0.041). Conclusions- Perforator stroke after basilar artery stenting may be related to negative remodeling on high-resolution magnetic resonance imaging. The finding needs to be confirmed in future studies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02705599.

Coronary Plaque Geometry and Thoracic Fat Distribution in Patients with Acute Chest Pain – a CT Angiography Study

Abstract The aim of our study was to investigate the correlation between volumes of thoracic fat distributed in different compartments and the geometry of vulnerable coronary plaques assessed by coronary computed tomography angiography (CCTA), in patients with acute chest pain. Methods: This was a non-randomized, observational, single-center study, including 50 patients who presented in the emergency department with acute chest pain who underwent 128-slice single-source CCTA. Plaque geometry was evaluated in transversal and longitudinal planes, and the assessment of adipose tissue was performed using the Syngo.via Frontier (Siemens AG, Healthcare Sector, Forchheim, Germany) research platform. Results: Eccentric plaques presented a significantly higher incidence of spotty calcification (40% vs. 22%, p = 0.018), whereas positive remodeling, volume of low attenuation plaque, and incidence of napkin-ring sign were not significantly different between the study groups or in ascending versus descending plaques. The volume of pericoronary fat around the plaque was significantly larger near eccentric lesions (707.68 ± 454.08 mm3 vs. 483.25 ± 306.98 mm3, p = 0.046) and descendent plaques (778.26 ± 479.37 mm3 vs. 473.60 ± 285.27 mm3, p = 0.016). Compared to ascending lesions, descendent ones presented a significantly larger volume of thoracic fat (1,599.25 ± 589.12 mL vs. 1,240.71 ± 291.50 mL), while there was no significant correlation between thoracic fat and cross-sectional eccentricity. Conclusions: The phenotype of plaque distribution and geometry seems to be associated with a higher vulnerability of coronary lesions and may be influenced by the local accumulation of inflammatory mediators released by the pericoronary epicardial adipose tissue.

Three-dimensional quantitative analysis of amyloid plaques in the whole brain with high voxel resolution

Amyloidosis of the central nervous system is one of the main pathological hallmarks of Alzheimer’s disease (AD). Changes in the number and the load of amyloid plaque (Aβ) deposition are important indicators of the progression of AD. However, the quantitative analysis of amyloidosis at the subcellular level in the whole brain remains a substantial challenge. In this study, an automatic analysis method was established for assessing amyloid plaques in the whole brain, including convenient whole brain labeling, imaging with a fluorescence micro-optical sectioning tomography system (fMOST) and an automated three-dimensional (3D) analysis method. Validation using immunostaining showed that the detection rate of amyloid plaques larger than 10 µm was 97.71%±0.18%. We achieved a 3D dataset of amyloid plaques in the whole brain of a 5XFAD transgenic mouse at a resolution of 0.32 μm×0.32 μm×2 μm and quantitatively analyzed the 3D distribution of amyloid plaques in different brain regions and nuclei through automated registration, segmentation and counting. The results indicated that the combination of the fMOST system with a whole brain staining method enables the acquisition and quantitative analysis of a brain-wide dataset of amyloid plaques, which may contribute to elucidating the underlying pathogenesis of AD and therapeutic drug discovery.

The prevalence of myocardial bridging on multidetector computed tomography and its relation to coronary plaques.

PurposeTo test the hypothesis that the prevalence of myocardial bridging varies between ethnic groups, and that the segment proximal to the myocardial bridge is more prone to plaque formation.Material and methodsA total of 4500 patients who had undergone computerised tomography (CT) coronary angiography at our institute were studied for myocardial bridging. Data on the clinical profile and indication for CT coronary angiography in myocardial bridging were collected. Patients with and without proximal disease were compared using the chi-square test for ordinal variables and Student’s t-test for continuous variables. The length to depth ratio (RA-MA ratio) of the bridged segment was determined.ResultsThe prevalence of atherosclerotic plaques in the segment proximal to the bridged segment was 37.8%, which was lower than the prevalence of 48.7% for plaques in the corresponding segments among patients without myocardial bridging. The average length of the bridged segment was 15.5 ± 5 mm, and that for patients with and without proximal plaques was 13 ± 4 and 16 ± 6 mm (p = 0.1), respectively. Similarly, the average depth of the segments with and without proximal plaques was 1.8 ± 0.6 mm and 1.4 ± 0.5 mm (p = 0.06), respectively. Only the RA-MA ratio (8 ± 3 vs. 13 ± 6, p = 0.01) was significantly lower in patients with atherosclerotic plaques.ConclusionsThe prevalence in our study population was 10%, with mid left anterior descending artery (LAD) being the most common segment involved. Moreover, the prevalence and distribution of coronary plaques in LAD were similar in patients with and without myocardial bridging.

Improvement of dose distribution in ocular brachytherapy with 125I seeds 20-mm COMS plaque followed to loading of choroidal tumor by gold nanoparticles.

Brachytherapy using removable ophthalmic plaques loaded with suitable small sealed radioactive seeds adjacent to the ocular's tumor has been widely used as an effective treatment. The aim of this study was to investigate the dose distribution in a modeled eyeball followed to loading of an ocular melanoma tumor with different concentrations of gold nanoparticles (GNPs) as dose enhancement agent by Monte Carlo (MC) calculations. The MC code of MCNPX 2.6.0 was used to modeling of COMS standard eye plaque loaded with 24 125I sources (6711 model) located on the sclera of modeled eyeball with detailed structures and materials. A choroidal melanoma tumor was simulated and loaded with different concentrations of spherical gold GNPs (50 nm in diameter). Dose enhancement factors (DEFs) of ocular components were calculated. The dosimetric properties of 125I source (6711 model) and dose distribution of COMS standard eye plaque were calculated successfully as recommended by TG-43U1; AAPM. Loading of tumor with GNPs increased dose to the tumor and decreased dose to the normal tissues; the DEF was increased up to 2.280 and 2.030 for tumor apex, while it was decreased to 0.760 and 0.892 for macula and for gold-tumor mixture and nanolattice distributions, respectively. Loading the choroidal tumor volume with GNPs improves the dose distribution by increasing dose to the tumor and decreasing dose to the health components in ocular brachytherapy with 125I seeds 20-mm COMS plaque.

Misery perfusion and amyloid deposition in atherosclerotic major cerebral artery disease.

Although experimental studies have shown that global cerebral hypoperfusion leads to amyloid deposition in the hemisphere with carotid artery occlusion in rodents, the results of such occurrence are controversial in humans. Hence, we aim to determine whether global cerebral hypoperfusion leading to decreased blood flow relative to metabolic demand [increased oxygen extraction fraction (OEF), misery perfusion] is associated with increases in amyloid deposition in the hemisphere with atherosclerotic major cerebral artery disease in patients. We evaluated the distribution of β-amyloid plaques using positron emission tomography and a [18F]-pyridylbenzofuran derivative (18F-FPYBF-2) in 13 patients with unilateral atherosclerotic disease of the internal carotid artery (ICA) or middle cerebral artery (MCA) disease and no cortical infarction. The distribution volume ratio (DVR) of 18F- FPYBF-2 was calculated using dynamic data and Logan graphical analysis with reference tissue and was correlated with the cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and OEF, obtained from 15O-gas PET. The mean cortical value was calculated as the mean value within the frontal, posterior cingulate, precuneus, parietal, and lateral temporal cortical regions. Significant reductions in CBF and CMRO2 and increases in OEF were found in the hemisphere ipsilateral to the arterial lesion compared with the contralateral hemisphere. There was no significant difference for 18F-FPYBF-2 DVR between hemispheres. The ipsilateral to contralateral ratio of the 18F- FPYBF-2 DVR was increased in 3 patients, while the ipsilateral to contralateral OEF ratio was increased in 4 patients. The incidence of an increased hemispheric DVR ratio was significantly higher in patients with an increased hemispheric OEF ratio (3/4) than in patients without (0/9) (p < 0.02). Although the 18F- FPYBF-2 DVR in the ipsilateral hemisphere was positively correlated with OEF after adjustment for the 18F- FPYBF-2 DVR in the contralateral hemisphere using multiple regression analysis (p < 0.05), the contribution rate of OEF was small (R2 = 5.5%). Only one of the 4 patients with an increased hemispheric OEF ratio showed amyloid positivity based on the DVR value. In atherosclerotic major cerebral artery disease, misery perfusion accompanied only small increases of amyloid deposition at best. Misery perfusion was not associated with amyloid positivity.

Atherosclerotic plaque burden evaluated from neck to groin: effect of gender and cardiovascular risk factors.

We explored the impact of gender and cardiovascular risk factors (RF) in the distribution and burden of coronary and extra-coronary atherosclerotic plaques among patients undergoing ECG-gated thoracoabdominal computed tomography angiography (CTA) from the supra-aortic trunks to the femoral arteries. We included a consecutive cohort of patients who underwent ECG-gated thoracoabdominal aortic CTA from the supra-aortic trunks to the pubic symphysis. We evaluated the number of coronary segments with plaques [segment-involvement score (SIS)]; and the extra-coronary atherosclerotic plaque burden, comprising the aorta and supra-aortic trunks, iliofemoral arteries, and visceral arteries (extra-coronary SS). A total of 3400 vascular segments were evaluated in 100 patients (mean age 67.0 ± 12.6 years, 66% male). Seventy-two (72%) patients had evidence of atherosclerosis in the coronary tree (coronary SIS ≥ 1), of which 32% was extensive (coronary SIS > 5). Males had a significantly higher prevalence of coronary SIS ≥ 1 [53 (80%), vs. 19 (56%), p = 0.018], and coronary SIS > 5 [24 (36%) vs. 8 (24%), p = 0.035] than females. Extra-coronary SS was similar between genders (males 10.2 ± 5.8 vs. females 9.7 ± 5.4, p = 0.70), irrespective of the location along the different vascular beds. The number of coronary RF was significantly related to the coronary SIS (p = 0.038), and hypertension and diabetes were consistently related to coronary and extra-coronary plaque burden. In the present study involving analysis of multiple vascular beds from the supra-aortic trunks to the femoral arteries, we identified significant sex-related differences in coronary plaque burden, whereas extra-coronary plaque burden was similar between genders irrespective of the vascular bed assessed.

Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease.

A variety of Alzheimer's disease (AD) mouse models overexpress mutant forms of human amyloid precursor protein (APP), producing high levels of amyloid β (Aβ) and forming plaques. However, the degree to which these models mimic spatiotemporal patterns of Aβ deposition in brains of AD patients is unknown. Here, we mapped the spatial distribution of Aβ plaques across age in three APP-overexpression mouse lines (APP/PS1, Tg2576, and hAPP-J20) using in vivo labeling with methoxy-X04, high throughput whole brain imaging, and an automated informatics pipeline. Images were acquired with high resolution serial two-photon tomography and labeled plaques were detected using custom-built segmentation algorithms. Image series were registered to the Allen Mouse Brain Common Coordinate Framework, a 3D reference atlas, enabling automated brain-wide quantification of plaque density, number, and location. In both APP/PS1 and Tg2576 mice, plaques were identified first in isocortex, followed by olfactory, hippocampal, and cortical subplate areas. In hAPP-J20 mice, plaque density was highest in hippocampal areas, followed by isocortex, with little to no involvement of olfactory or cortical subplate areas. Within the major brain divisions, distinct regions were identified with high (or low) plaque accumulation; for example, the lateral visual area within the isocortex of APP/PS1 mice had relatively higher plaque density compared with other cortical areas, while in hAPP-J20 mice, plaques were densest in the ventral retrosplenial cortex. In summary, we show how whole brain imaging of amyloid pathology in mice reveals the extent to which a given model recapitulates the regional Aβ deposition patterns described in AD.

Morphologic characteristics of severe basilar artery atherosclerotic stenosis on 3D high-resolution MRI

BackgroundTwo-dimensional high-resolution MRI (2D HRMRI) faces many technical challenges for fully assessing morphologic characteristics of inherent tortuous basilar arteries. Our aim was to investigate remodeling mechanisms and plaque distribution in symptomatic patients with basilar artery stenosis on three-dimensional (3D) HRMRI.MethodsForty-six consecutive patients with symptomatic basilar artery atherosclerotic stenosis on MRA (70–99%) were enrolled. The remodeling index (RI) was the ratio of vessel area at the maximal-lumen-narrowing (MLN) site to reference vessel area. RI ≥ 1.05 was defined as positive remodeling (PR), RI ≤ 0.95 as negative remodeling (NR), and 0.95 < RI < 1.05 as intermediate remodeling (IR). The remodeling patterns were divided into two groups (PR and non-PR [NR and IR]). The cross-sectional and longitudinal distribution of BA plaques were evaluated.ResultsTwo patients were excluded because of poor-quality images. Images of 44 patients were available for measurements. PR was found in 23 (52.3%) patients, and non-PR in 21 (47.7%) patients. At the MLN sites, vessel area, wall area, plaque size and percentage of plaque burden of PR group were significantly greater than non-PR group (p < .001). Most plaques (90.9%) of the 44 patients were located at the dorsal, left and right walls. For the longitudinal distribution of plaque, 8 (18.2%) and 36 (81.8%) plaques were located in BA proximal and distal to AICA, respectively. Most plaques (68.2%) were eccentrically distributed.Conclusions3D HRMRI with postprocessing multiple planar reconstruction is able to evaluate the remodeling pattern and plaque distribution of basilar artery atherosclerotic stenosis, which might be used to guide intracranial intervention.

New Insights into the Spontaneous Human Alzheimer's Disease-Like Model Octodon degus: Unraveling Amyloid-β Peptide Aggregation and Age-Related Amyloid Pathology.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Despite advances in our understanding of the molecular milieu driving AD pathophysiology, no effective therapy is currently available. Moreover, various clinical trials have continued to fail, suggesting that our approach to AD must be revised. Accordingly, the development and validation of new models are highly desirable. Over the last decade, we have been working with Octodon degus (degu), a Chilean rodent, which spontaneously develops AD-like neuropathology, including increased amyloid-β (Aβ) aggregates, tau hyperphosphorylation, and postsynaptic dysfunction. However, for proper validation of degu as an AD model, the aggregation properties of its Aβ peptide must be analyzed. Thus, in this study, we examined the capacity of the degu Aβ peptide to aggregate in vitro. Then, we analyzed the age-dependent variation in soluble Aβ levels in the hippocampus and cortex of third- to fifth-generation captive-born degu. We also assessed the appearance and spatial distribution of amyloid plaques in O. degus and compared them with the plaques in two AD transgenic mouse models. In agreement with our previous studies, degu Aβ was able to aggregate, forming fibrillar species in vitro. Furthermore, amyloid plaques appeared in the anterior brain structures of O. degus at approximately 32 months of age and in the whole brain at 56 months, along with concomitant increases in Aβ levels and the Aβ42/Aβ40 ratio, indicating that O. degus spontaneously develops AD-like pathology earlier than other spontaneous models. Based on these results, we can confirm that O. degus constitutes a valuable model to improve AD research.

Different Patterns of Neurodegeneration and Glia Activation in CA1 and CA3 Hippocampal Regions of TgCRND8 Mice.

We investigated the different patterns of neurodegeneration and glia activation in CA1 and CA3 hippocampal areas of TgCRND8 mice. The main feature of this transgenic model is the rapid development of the amyloid pathology, which starts already at 3 months of age. We performed immunohistochemical analyses to compare the different sensibility of the two hippocampal regions to neurodegeneration. We performed qualitative and quantitative evaluations by fluorescence immunohistochemistry with double or triple staining, followed by confocal microscopy and digital image analysis in stratum pyramidale (SP) and stratum radiatum (SR) of CA1 and CA3, separately. We evaluated time-dependent Aβ plaques deposition, expression of inflammatory markers, as well as quantitative and morphological alterations of neurons and glia in transgenic mice at 3 (Tg 3M) and 6 (Tg 6M) months of age, compared to WT mice. In CA1 SR of Tg 6M mice, we found significantly more Medium and Large plaques than in CA3. The pattern of neurodegeneration and astrocytes activation was different in the two areas, indicating higher sensitivity of CA1. In the CA1 SP of Tg 6M mice, we found signs of reactive astrogliosis, such as increase of astrocytes density in SP, increase of GFAP expression in SR, and elongation of astrocytes branches. We found also common patterns of glia activation and neurodegenerative processes in CA1 and CA3 of Tg 6M mice: significant increase of total and reactive microglia density in SP and SR, increased expression of TNFα, of iNOS, and IL1β in astrocytes and increased density of neurons–astrocytes–microglia triads. In CA1 SP, we found decrease of volume and number of pyramidal neurons, paralleled by increase of apoptosis, and, consequently, shrinkage of CA1 SP. These data demonstrate that in TgCRND8 mice, the responses of neurons and glia to neurodegenerative patterns induced by Aβ plaques deposition is not uniform in the two hippocampal areas, and in CA1 pyramidal neurons, the higher sensitivity may be related to the different plaque distribution in this area. All these modifications may be at the basis of memory loss, the peculiar symptom of AD, which was demonstrated in this transgenic mouse model of Aβ deposition, even at early stages.

Abstract 17183: Genetically Engineered Calcification Increases Surface Roughness and Changes the Distribution of Atherosclerotic Plaques in Mice With Atherosclerosis

Background: Atherosclerosis is an inflammatory disease that contributes significantly to cardiovascular mortality. Arterial stiffening due to calcification can coexist with or directly influence pathogenesis of atherosclerosis. We hypothesize that arteriosclerosis caused by genetically engineered calcification in mice redistributes shear stress on the endothelial cells, which in turn leads to further accelerated rate of plaque formation. Methods: All of the mice had an LDL receptor mutation and were fed pro-atherogenic diet (1.25% cholesterol). The case group overexpressed tissue-nonspecific alkaline phosphatase in endothelial cells (eTNAP). The luminal surfaces of descending thoracic aorta (TA) and suprarenal abdominal aorta (AA) were scanned using Sensofar S Neox optical confocal microscope at 1 μm vertical resolution. The surface topographies per sample, each measuring 500 x 700 microns, were analyzed for ISO 25178-2 areal roughness parameters using SensoMap. Parameters were compared by t test (n=5 eTNAP, n=6-7 control). Results: We observed a significant difference in the incidence as well as the morphology of the plaques in the eTNAP group compared to control mice. There was a 4.8 fold increase in the number of topological motifs in the thoracic aorta of the eTNAP vs. controls (p &lt; 0.01). Similarly, the number of motifs was increase in the abdominal aorta of the eTNAP mice compared to controls (2.8 fold; p=0.06). The average area of the motifs was significantly larger in the controls compared to the eTNAP group in both segments of the aorta (p=0.06 TA; p &lt; 0.05 AA). The maximum height of the lesions in the TA was not different between the groups (p=0.62), however increased by 74% in the abdominal aorta of the eTNAP compared to controls (p&lt;0.05). Finally, the surface developed interfacial area ratio (Sdr, a parameter of texture) was increased in the eTNAP group in both the TA (p &lt; 0.05) and AA regions (p &lt; 0.01). Conclusion: Arteriosclerosis increases surface roughness. In our model, the abdominal region had a high incidence of taller, irregular lesions whereas those in the thoracic aorta were flatter and more spaced. The high resolution scans will be further used to study the hemodynamic disturbances to the endothelial cells using flow dynamics simulations.

Symmetrical acral keratoderma revisited: proposal for a new term, 'pigmented carpotarsal hyperkeratosis'.

First reported from Taiwan mistakenly as acral acanthosis nigricans in 1991, pigmented carpotarsal hyperkeratosis or hyperkeratosis nigricans carpi et tarsi displays a peculiar distribution of velvety brown-grey hyperpigmented plaques symmetrically on the flexural side of the wrists and ankles and on the dorsal sides of the hands and feet. A marked epidermal hyperkeratosis with typically mild acanthosis and papillomatosis is observed in histology. Whitish maceration upon perspiration or water exposure, with exacerbation in summer but remission in winter, is common. The association with obesity, endocrine disorders, atopic dermatitis, ichthyosis or malignancy is unknown. Familial occurrence and hereditary patterns are ill-defined. There is preliminary evidence indicating a pathogenic role of missense mutation in the transcription factor 4 gene. Treatment is empirical, with good outcome with topical retinoids and keratolytic agents. Recurrence is common, and long-term prognosis is unclear. To be distinguished are acral acanthosis nigricans, palmoplantar keratoderma of the Nagashima type, palmoplantar keratoderma of the Bothnian type and aquagenic palmoplantar keratoderma. Most reported cases are from Southern China and are predominantly observed in men between the ages of 20 and 40 years. The currently used term 'symmetrical acral keratoderma' is non-specific and misleading and may lead to global unawareness, underreporting or misdiagnosis of this phenomenon. Further genetic and molecular studies are required to clarify its pathogenesis and relation to palmoplantar keratoderma.

Middle cerebral artery geometric features are associated with plaque distribution and stroke.

We aimed to investigate the geometric features of the middle cerebral artery (MCA) and their relevance to plaque distribution and ischemic stroke. We reviewed our institutional vessel wall imaging database. Patients with symptomatic MCA atherosclerosis, asymptomatic MCA atherosclerosis, or without MCA atherosclerosis were included. The MCA geometric features, including M1 segment shape and M1 curve orientation, were defined on magnetic resonance angiography. Plaque distribution and other plaque parameters were identified on vessel wall imaging. The association among MCA geometric features, plaque distribution, and ischemic stroke were analyzed. A total of 977 MCAs were analyzed (87 atherosclerotic symptomatic MCAs, 459 atherosclerotic asymptomatic MCAs, and 431 plaque-free MCAs). Overall, curved M1 segments were the predominant shape across all groups. In 91.1% of curved atherosclerotic MCAs, the plaque involved the inner wall of the curve. Plaque not involving the inner wall was shorter (p < 0.0001) and thinner (p = 0.005) compared to plaque involving the inner wall. Inferior plaque was observed in 39.9% of inferior-oriented M1 curves compared to 21.7% in non-inferior-oriented M1 curves (p < 0.0001). The absence of an inferior-oriented M1 curve (odds ratio 0.45, 95% confidence interval 0.27-0.77) and presence of superior plaque (odds ratio 2.67, 95% confidence interval 1.52-4.67) were independently associated with stroke after adjusting for plaque length and thickness, degree of stenosis, and remodeling ratio. MCA geometric features are associated with plaque distribution and stroke. Our findings provide insight into the vascular pathophysiology of MCA atherosclerosis.

TCT-54 The distribution of high-risk plaques with respect to artery stenosis in non-culprit non-ischemic native coronary lesions of diabetic patients – data from COMBINE OCT-FFR study

Thin fibrous cap atheroma (TCFA), plaque rupture (PR), plaque erosion (PE) triggers the acute coronary syndrome. However, the prevalence of these plaques in non-ischemic lesions in diabetes mellitus (DM) patients was barely reported. This report presents the distribution of high-risk plaques in non-

TCT-333 ROLE OF OPTICALCOHERENCE TOMOGRAPHY ACKNOWLEDGED FOR LEFT MAIN STEM ANGIOPLASTY. The ROCK Cohort I study.

Percutaneous treatment of left main (LM-PCI) coronary artery disease has gained strong scientific evidence sharing a similar outcome to coronary artery bypass in patients with low or intermediate Syntax scores. This lesion setting has several anatomical characteristics (plaque type and distribution

Estimation of amyloid distribution by [18F]flutemetamol PET predicts the neuropathological phase of amyloid \u03b2-protein deposition

The deposition of the amyloid β-protein (Aβ) in senile plaques is one of the histopathological hallmarks of Alzheimer’s disease (AD). Aβ-plaques arise first in neocortical areas and, then, expand into further brain regions in a process described by 5 phases. Since it is possible to identify amyloid pathology with radioactive-labeled tracers by positron emission tomography (PET) the question arises whether it is possible to distinguish the neuropathological Aβ-phases with amyloid PET imaging. To address this question we reassessed 97 cases of the end-of-life study cohort of the phase 3 [18F]flutemetamol trial (ClinicalTrials.gov identifiers NCT01165554, and NCT02090855) by combining the standardized uptake value ratios (SUVRs) with pons as reference region for cortical and caudate nucleus-related [18F]flutemetamol-retention. We tested them for their prediction of the neuropathological pattern found at autopsy. By defining threshold levels for cortical and caudate nucleus SUVRs we could distinguish different levels of [18F]flutemetamol uptake termed PET-Aβ phase estimates. When comparing these PET-Aβ phase estimates with the neuropathological Aβ-phases we found that PET-Aβ phase estimate 0 corresponded with Aβ-phases 0-2, 1 with Aβ-phase 3, 2 with Aβ-phase 4, and 3 with Aβ-phase 5. Classification using the PET-Aβ phase estimates predicted the correct Aβ-phase in 72.16% of the cases studied here. Bootstrap analysis was used to confirm the robustness of the estimates around this association. When allowing a range of ± 1 phase for a given Aβ-phase correct classification was given in 96.91% of the cases. In doing so, we provide a novel method to convert SUVR-levels into PET-Aβ phase estimates that can be easily translated into neuropathological phases of Aβ-deposition. This method allows direct conclusions about the pathological distribution of amyloid plaques (Aβ-phases) in vivo. Accordingly, this method may be ideally suited to detect early preclinical AD-patients, to follow them with disease progression, and to provide a more precise prognosis for them based on the knowledge about the underlying pathological phase of the disease.

Preoperative Assessment of Coronary Arteries by Cardiac Computed Tomography in Patients with Lung Cancer.

To retrospectively evaluate characteristics of coronary artery disease (CAD) in patients undergoing lung resection for cancer by using dual-source computed tomography (DSCT), thus increasing our understanding of perioperative evaluation. DSCT coronary angiography was performed for perioperative evaluation in 145 patients with non-small cell lung cancer (NSCLC) due to suspected CAD. The imaging characteristics of CAD including extent, distribution and types of plaques, and luminal stenosis and congenial anomalous including origin of coronary arteries and myocardial bridge (MB) were evaluated and compared by sex, smoking behavior, and pathological types. In total, coronary artery plaques were observed in 130 (89.7%) patients. A total of 205 coronary vessels (1.7 ± 1.3 per patient) and 278 segments (2.4 ± 2.3 per patient) were found to have plaques, respectively. The most frequently involved segment were the left anterior descending (LAD) artery (45.4%) and its proximal segment (24.1%) (p < 0.05). Mild narrowing (61.7%) and calcified plaques (52.9%) were most found (all p < 0.001). Types of plaques, luminal narrowing and extent were not significantly different by sex, smoking behavior, or pathological type. Anomalous origination of the right coronary ostium from left sinus was observed in 0.7% of patients. MB was observed in 16.6% of patients. Dual-source CT is a useful preoperative noninvasive test for CAD in patients planning to undergo lung resection for cancer.

Studiu privind distribuţia plăcii microbiene la nivelul suprafeţelor dentare

Studiu privind distribuţia plăcii microbiene la nivelul suprafeţelor dentare

Discovery of a Novel Periodontal Disease-Associated Bacterium

One of the world’s most common infectious disease, periodontitis (PD), derives from largely uncharacterized communities of oral bacteria growing as biofilms (a.k.a. plaque) on teeth and gum surfaces in periodontal pockets. Bacteria associated with periodontal disease trigger inflammatory responses in immune cells, which in later stages of the disease cause loss of both soft and hard tissue structures supporting teeth. Thus far, only a handful of bacteria have been characterized as infectious agents of PD. Although deep sequencing technologies, such as whole community shotgun sequencing have the potential to capture a detailed picture of highly complex bacterial communities in any given environment, we still lack major reference genomes for the oral microbiome associated with PD and other diseases. In recent work, by using a combination of supervised machine learning and genome assembly, we identified a genome from a novel member of the Bacteroidetes phylum in periodontal samples. Here, by applying a comparative metagenomics read-classification approach, including 272 metagenomes from various human body sites, and our previously assembled draft genome of the uncultivated Candidatus Bacteroides periocalifornicus (CBP) bacterium, we show CBP’s ubiquitous distribution in dental plaque, as well as its strong association with the well-known pathogenic “red complex” that resides in deep periodontal pockets.