Noncalcified Segments Research Articles

High Tyrosol and Hydroxytyrosol Intake Reduces Arterial Inflammation and Atherosclerotic Lesion Microcalcification in Healthy Older Populations.

Aging is an important risk factor for cardiovascular diseases and convincing data have shown that chronic low-grade inflammation, which develops with advanced age, contributes significantly to cardiovascular risk. The present study aimed to use 18F-FDG/18F-NaF-PET/CT imaging to, respectively, gauge arterial inflammation and microcalcification in a healthy elderly population and to assess the potential benefits of a tyrosol- and hydroxytyrosol-rich diet on these two markers of atherosclerotic plaque fragility. Eleven healthy participants (mean age 75 ± 5.67 years) were supplemented for 6 months with high polyphenol-rich extra virgin olive oil (HP-EVOO), extra virgin olive oil (EVOO), or refined olive oil (ROO). The participants underwent PET/CT imaging with 18F-FDG and 18F-NaF radiotracers at baseline and after 6 months. 18F-FDG and 18F-NaF uptakes were quantified using standardized uptake values (SUV) and were categorized based on artery calcification and olive oil type. A total of 324 slices of the aortas of the imaged participants were analyzed for arterial inflammation and 327 slices were analyzed for microcalcification. 18F-FDG uptake was significantly higher in the non-calcified segments than in the calcified segments (SUVmax = 2.70 ± 0.62 and SUVmax = 2.54 ± 0.44, respectively, p < 0.042). Conversely, the non-calcified segments displayed significantly lower 18F-NaF uptake than the calcified segments (SUVmax = 1.90 ± 0.37 and 2.09 ± 0.24, respectively, p < 0.0001). The 6-month supplementation with HP-EVOO induced a significant reduction in 18F-FDG uptake in both the non-calcified (2.93 ± 0.23 to 2.75 ± 0.38, p < 0.004) and calcified segments of the aortas (2.25 ± 0.29 to 2.15 ± 0.19, p < 0.02). 18F-NaF uptake was also significantly lower in patients supplemented with HP-EVOO (SUVmax = 1.98 ± 0.33 at baseline compared to 1.85 ± 0.28, after the 6-month supplementation, p < 0.004), whereas no significant effect was observed with EVOO. Conversely, participants supplemented with ROO displayed a significant increase in 18F-NaF uptake (SUVmax = 1.78 ± 0.34 to 1.95 ± 0.34, p < 0.0001). The present study confirmed that a phenolic-compound-rich diet reduces both arterial inflammation and atherosclerotic lesion microcalcification and demonstrated that 18F-FDG/18F-NaF-PET/CT imaging is a valuable approach for assessing age-related arterial damage.

Non-calcified active atherosclerosis plaque detection with 18F-NaF and 18F-FDG PET/CT dynamic imaging.

Arterial inflammation is an indicator of atheromatous plaque vulnerability to detach and to obstruct blood vessels in the heart or in the brain thus causing heart attack or stroke. To date, it is difficult to predict the plaque vulnerability. This study was aimed to assess the behavior of 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake in the aorta and iliac arteries as a function of plaque density on CT images. We report metabolically active artery plaques associated to inflammation in the absence of calcification. 18 elderly volunteers were recruited and imaged with computed tomography (CT) and positron emission tomography (PET) with 18F-NaF and 18F-FDG. A total of 1338 arterial segments were analyzed, 766 were non-calcified and 572 had calcifications. For both 18F-NaF and 18F-FDG, the mean SUV values were found statistically significantly different between non-calcified and calcified artery segments. Clustering CT non-calcified segments, excluding blood, resulted in two clusters C1 and C2 with a mean density of 30.63 ± 5.06 HU in C1 and 43.06 ± 4.71 HU in C2 (P < 0.05), and their respective SUV were found statistically different in 18F-NaF and 18F-FDG. The 18F-NaF images showed plaques not detected on CT images, where the 18F-FDG SUV values were high in comparison to artery walls without plaques. The density on CT images alone corresponding to these plaques could be further investigated to see whether it can be an indicator of the active plaques.

Differential proteome profile, biological pathways, and network relationships of osteogenic proteins in calcified human aortic valves.

Calcific aortic valve disease (CAVD) is the most common heart valve disease requiring intervention. Most research on CAVD has focused on inflammation, ossification, and cellular phenotype transformation. To gain a broader picture into the wide range of cellular and molecular mechanisms involved in this disease, we compared the total protein profiles between calcified and non-calcified areas from 5 human valves resected during surgery. The 1413 positively identified proteins were filtered down to 248 proteins present in both calcified and non-calcified segments of at least 3 of the 5 valves, which were then analyzed using Ingenuity Pathway Analysis. Concurrently, the top 40 differentially abundant proteins were grouped according to their biological functions and shown in interactive networks. Finally, the abundance of selected osteogenic proteins (osteopontin, osteonectin, osteocalcin, osteoprotegerin, and RANK) was quantified using ELISA and/or immunohistochemistry. The top pathways identified were complement system, acute phase response signaling, metabolism, LXR/RXR and FXR/RXR activation, actin cytoskeleton, mineral binding, nucleic acid interaction, structural extracellular matrix (ECM), and angiogenesis. There was a greater abundance of osteopontin, osteonectin, osteocalcin, osteoprotegerin, and RANK in the calcified regions than the non-calcified ones. The osteogenic proteins also formed key connections between the biological signaling pathways in the network model. In conclusion, this proteomic analysis demonstrated the involvement of multiple signaling pathways in CAVD. The interconnectedness of these pathways provides new insights for the treatment of this disease.

Light Absorption in Coralline Algae (Rhodophyta): A Morphological and Functional Approach to Understanding Species Distribution in a Coral Reef Lagoon

Red coralline algae are a cosmopolitan group with the ability to precipitate CaCO3 within the walls of their vegetative cells. The resultant carbonate structure is key for explaining their ecological success, as it provides protection against herbivores and resistance to water motion. However, its potential contribution to enhance thallus light absorption efficiency through multiple light scattering on algal skeleton, similar to the effect documented for scleractinian corals, has not been yet investigated. Here, we initiate this analysis, characterizing thallus optical properties of three coralline species, which differed in pigment content and thallus mass area (TMA, gDW m-2). The three species, the rhodolith Neogoniolithon sp., the crustose coralline alga (CCA), Lithothamnion sp., and the articulated alga Amphiroa tribulus, represent the more distinctive coralline growth-forms and were able to colonize contrasting light environments in Caribbean coral reefs. The thicker thalli of the rhodoliths were the most efficient light collectors, as evidenced by their higher pigment absorption efficiency (a*Chla; m2 mgChla-1) and photosynthetic rates per unit area. This could explain rhodolith success in oligotrophic, highly illuminated reef environments. In contrast, the thinner thalli of the CCA, a low-light specialist, showed the highest metabolic rates normalized to mass and the highest light absorption efficiencies per unit mass (a*M; m2 gdw-1). Therefore, the ecological success of the CCA in cryptic habitats within the reef cannot be explained only by its low-light physiology, but also by its capacity to reduce the structural costs of their thalli, and thus of its new growth. Lastly, the ecological success of Amphiroa tribulus, which displayed intermediate values for the efficiency of light absorption, metabolic rates and TMA, was explained by its ability to construct the largest light collectors (algal canopies) thanks to the presence of flexible, non-calcified segments (genicula). This ability enables enhanced photosynthetic and carbonate production at the organism/canopy level. The resulting fragile canopy survives best within the protection provided by colonies of the lettuce coral Agaricia agaricites. In conclusion, our study demonstrates the utility of optical traits as powerful tools to investigate differences in the competitive abilities, abundances and niche distribution among algal species and/or growth-forms.

Qualitative and quantitative diagnostic performance of 320-slice computed tomography for detecting coronary artery disease with respect to atherosclerotic plaque characteristics

To investigate qualitatively and quantitatively the diagnostic performance of 320-slice CT for detection of coronary artery disease with respect to different atherosclerotic plaque characteristics. A retrospective search was performed for inpatients underwent both coronary CT and further coronary angiography (CAG) from December 1, 2008 to December 31, 2012. The diagnostic performance of 320-slice CTA for detecting significant stenosis ( ≥ 50% diameter) with respect to atherosclerotic plaque characteristics were analyzed by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, kappa index (κ), and area under the receiver operating characteristic curve (AUC). Chi-square test was used to evaluate whether there were significant differences of the true-case frequency (true positive + true negative) and false-case frequency (false positive + false negative) among groups. Bland-Altman analysis was used to determine limits of agreement between CTA and CAG. A total of 454 patients and 6 779 segments were analyzed. Diagnostic accuracy was higher in non-calcified segments; whereas they decreased in the presence of both mild-moderately and heavily calcified plaques. Excellent agreement (κ = 0.810) between CT and CAG was observed for non-calcified segments, while good agreement was observed for both mild-moderately (κ = 0.701) and heavily calcified segments (κ = 0.750). Both mild-moderate (P = 0.000) and heavy (P = 0.000) calcification decreased the true-case frequency and increased the false-case frequency when compared to non-calcification. There were no significant underestimation or overestimation for non-calcified (P = 0.087) and mild-moderately calcified (P = 0.704) segments, while there was significant overestimation for heavily calcified segments (P = 0.001). Great qualitative and quantitative diagnostic performances of 320-slice CT were observed in non-calcified coronary segments. However, qualitative diagnostic performance decreased in both mild-moderately and heavily calcified segments, and quantitative overestimation were observed in heavily calcified segments.

Diagnostic accuracy of computed tomography coronary angiography for evaluation of coronary artery disease: a comparison between high definition versus standard definition scanner

Background: The ability of computed tomography coronary angiography (CTCA) to detect quantitatively the stenosis is lower than invasive coronary angiography (ICA) due to the limited spatial resolution and it could be responsible of a false positive rate of up to 35%. Recently, a high-definition CTCA (HDCTCA) scanner, with improved in-plane spatial resolution of 230 μm has been developed. The aim of this study is to compare the diagnostic accuracy by HDCTCA with standard definition 64-slice scanner (SDCTCA) by using ICA as the reference method. Methods: One-hundred-forty consecutive patients (mean age 65±8 years, male 105) scheduled for ICA were randomized to SDCTCA (n= 70, group 1) or HDCTCA-scan protocol (n= 70, group 2) (Discovery CT 750 HD scanner, GE Healthcare, Milwaukee, WI) before ICA. The scanning parameters were: slice acquisition 64x0.625 mm, gantry rotation time 330 msec and prospective ECG-triggering. We evaluated the Likert image quality (score 1: non-diagnostic to score 4: excellent), overall feasibility (Fe), the sensitivity (Se), specificity (Sp), negative predictive value (NPV), positive predictive value (PPV) and accuracy (Ac) versus ICA in a segment-based model and comparing the diagnostic performance between group 1 and group 2. Results: The 2 groups were homogeneous in terms of baseline characteristics. Group 2 showed a higher mean image quality score (3.8 vs 3.1, p<0.001) and overall evaluability (98% vs 92%, p<0.01) versus group 1, respectively. The Se, Sp, NPV, PPV, and accuracy were 89%, 94%, 96%, 83%, 93% and 93%, 97%, 98%, 93%, 96% in group 1 and group 2, respectively, including all segments censoring not-evaluable segments as positive. Group 2 showed a higher sensitivity and specifiivity and accuracy (p<0.05) but mainly a higher PPV (p<0.01) versus group 1. In a sub-analysis on calcified plaque the overall agreement between CTCA and ICA was lower in segments with calcification versus noncalcified segments in group 1 (p<0.01) while in group 2 there was no statistical difference between the overall agreement versus ICA based on the plaque composition. Conclusions: The present study showed an improved overall feasibility, positive predictive value and accuracy mainly in calcified coronary artery lesions in HDCTCA in comparison with SDCTCA due to the better spatial resolution and the consequent reduced blooming effect. Further studies are needed to compare the performance of HDCTCA versus the new dual-energy CT that offers a possible and alternative solution to the problem of heavily calcified coronary arteries reducing the overestimation of calcium volume.

石灰化病変の血管内腔評価における軌道同期ヘリカルスキャンを用いた下肢サブトラクションCT Angiographyの有用性

Massive calcification complicates the diagnosis of the blood vessel lumen in computed tomography angiography (CTA) of the arteries of the lower extremities. The purpose of this study was to evaluate subtraction CTA with the use of orbital synchronized helical scanning (OS-SCTA). Phantom study: We performed OS-SCTA and non-OSCTA of a calcified vessel phantom (ψ2.5 mm), and compared them with a non-calcified vessel phantom as the reference by full width at half maximum (FWHM) and full width at tenth maximum (FWTM) of maximum intensity projection (MIP) images. Clinical study: 58 patients with peripheral artery disease who were referred for angiography also underwent OS-SCTA. OS-SCTA was produced using MIP images. Findings were graded according to three categories: (1) stenosis greater than 50% or occluded; (2) stenosis less than 50%; (3) not detected due to insufficient image quality. OS-SCTA findings were compared with the angiographic findings for each arterial segment. In the phantom study, FWHM showed no significant difference between OS-SCTA and the reference (P=0.135), whereas FWTM showed a significant difference (P<0.001). FWHM and FWTM showed a significant difference between non-OS-SCTA and the reference (P<0.001), due to misregistration with helical artifacts. In a clinical study comparing OS-SCTA with angiography, the sensitivity and specificity were 93.3% and 95.1% in calcified segments, 91.8% and 93.9% in non-calcified segments, and 92.2% and 94.6% in all segments. There was no significant difference between calcified segments and non-calcified segments (sensitivity: P=0.568, specificity: P=0.549). OS-SCTA is beneficial for the diagnosis of lower extremity arteries with vessel wall calcification, since it shows detection accuracy comparable to that of angiography.

Laparoscopic Distal Pancreatectomy and Splenectomy for Malignant Tumors

Laparoscopic distal pancreatectomy has become the gold standard for benign tumors. As more surgeons have expertise in open and laparoscopic pancreatic surgery, increasing numbers of benign-appearing tumors are being removed via minimally invasive techniques and found to have malignancy on final pathology. Because of our growing experience in laparoscopic distal pancreatectomy, we have begun removing preoperatively suspected malignancies in the distal pancreas with minimally invasive techniques. All cases were collected prospectively in a database and analyzed retrospectively. All cases begun laparoscopically with the intention of performing the resection with minimally invasive techniques were considered even if the operation was ultimately converted to an open procedure. A total of 12 cases have been attempted of which four required hand assistance and one required conversion to an open approach due to delayed bleeding from a calcified splenic artery that had been transected with laparoscopic GIA stapler device. In total, eight (67%) patients had malignant disease and four (33%) were found to have benign tumors. The median lymph node retrieval is 8 (range 3-16) with no positive margins. The morbidity rate is 17% with one reoperation (8%) and one mortality (8%) at 30 and 90 days. The laparoscopic approach to malignant pancreatic tumors is feasible with similar morbidity and mortality rates to benign series. When tumors are next to the confluence of the splenic portal vein, a hand-assisted approach may be adviseable. Calcified splenic arteries should be sought on preoperative imaging and either transected in non-calcified segments or controlled via open techniques via the hand port.

Coronary Artery Stenoses: Accuracy of 64–Detector Row CT Angiography in Segments with Mild, Moderate, or Severe Calcification—A Subanalysis of the CORE-64 Trial

To evaluate the influence of cross-sectional arc calcification on the diagnostic accuracy of computed tomography (CT) angiography compared with conventional coronary angiography for the detection of obstructive coronary artery disease (CAD). Institutional Review Board approval and written informed consent were obtained from all centers and participants for this HIPAA-compliant study. Overall, 4511 segments from 371 symptomatic patients (279 men, 92 women; median age, 61 years [interquartile range, 53-67 years]) with clinical suspicion of CAD from the CORE-64 multicenter study were included in the analysis. Two independent blinded observers evaluated the percentage of diameter stenosis and the circumferential extent of calcium (arc calcium). The accuracy of quantitative multidetector CT angiography to depict substantial (≥ 50%) stenoses was assessed by using quantitative coronary angiography (QCA). Cross-sectional arc calcium was rated on a segment level as follows: noncalcified or mild (< 90°), moderate (90°-180°), or severe (> 180°) calcification. Univariable and multivariable logistic regression, receiver operation characteristic curve, and clustering methods were used for statistical analyses. A total of 1099 segments had mild calcification, 503 had moderate calcification, 338 had severe calcification, and 2571 segments were noncalcified. Calcified segments were highly associated (P < .001) with disagreement between CTA and QCA in multivariable analysis after controlling for sex, age, heart rate, and image quality. The prevalence of CAD was 5.4% in noncalcified segments, 15.0% in mildly calcified segments, 27.0% in moderately calcified segments, and 43.0% in severely calcified segments. A significant difference was found in area under the receiver operating characteristic curves (noncalcified: 0.86, mildly calcified: 0.85, moderately calcified: 0.82, severely calcified: 0.81; P < .05). In a symptomatic patient population, segment-based coronary artery calcification significantly decreased agreement between multidetector CT angiography and QCA to detect a coronary stenosis of at least 50%.

Multidetector-Row Computed Tomography in Evaluation of Atherosclerotic Carotid Plaques Complicated with Intraplaque Hemorrhage

Our aim was to determine the sensitivity and specificity of multidetector-row computed tomography (CT) in detecting atherosclerotic carotid plaques complicated with intraplaque hemorrhage. We examined carotid plaques from 31 patients operated for carotid artery stenosis. Results of preoperative multidetector-row CT analysis of carotid plaques were compared with results of histological analysis of the same plaque areas. Carotid endarterectomy was performed within 1 week of multidetector-row CT. American Heart Association classification of atherosclerotic plaques was applied for histological classification. Median tissue density of carotid plaques complicated with intraplaque hemorrhage was 22 Hounsfield units (HU). Median tissue density of noncalcified segments of uncomplicated plaques was 59 HU (p=0.0062). The highest tissue density observed for complicated plaques was 31 HU. Multidetector-row CT detected plaques complicated with hemorrhage with sensitivity of 100% and specificity of 64.7%, with tissue density of 31 HU as a threshold value. Multidetector-row CT showed a high level of sensitivity and a moderate level of specificity in detecting atherosclerotic carotid plaques complicated with hemorrhage.

Characteristics of coronary plaques before angiographic progression determined by Multi-Slice CT

The aim of the present study was to characterize coronary plaques by Multi-Slice Computed Tomography (Siemens sensation 16, Forcheim, Germany) before significant angiographic progression occurred and to compare them to non-progressing lesions. The MSCT-morphology of coronary plaques leading to a rapid angiographic disease progression is not yet studied. In a series of 68 patients who were scheduled for surveillance angiography 6 months later, MSCT-angiography was done shortly after the baseline catheterisation-procedure. After surveillance angiography rapid progressive lesions with an increase of the stenosis severity of >20% were identified and analysed on the baseline MSCT-scan and were compared to non-progressing lesions. Six months after coronary stenting we observed significant progression of de novo stenoses in 10/438 coronary segments. The progression of four lesions lead to angina pectoris symptoms and the remaining six lesions progressed silently. Analysis of the lesion morphology by MSCT revealed that 5/10 (50%) progressing lesions were non-calcified 3/10 (30%) were predominantly non-calcified and 2/10 (20%) were mainly calcified on the baseline MSCT-scan. In the 428 segments without disease progression atherosclerotic lesions were found in 225 segments on MSCT. Non-calcified plaques were identified in 46 (20%), predominantly non-calcified lesions in 58 (26%) and predominantly calcified lesions in 121 (54%) segments. The average number of diseased coronary segments between patients with and without lesion progression was not significantly different between progressors and non-progressors with a higher prevalence of non-calcified segments in the progressor group (1.1 vs. 0.63). Rapid progression of the angiographic stenosis severity during a 6 months period occurs most frequently in coronary segments revealing non-calcified or predominantly non-calcified plaques as determined by MSCT, whereas lesion progression is rare in predominantly calcified segments. This represents first evidence that non-calcified lesions may be involved in the process of plaque rupture.

Evaluation of coronary artery stenoses using electron-beam CT and multiplanar reformation.

We assessed the diagnostic value of electron-beam CT with multiplanar reformation for coronary artery stenoses. Thirty-seven patients who underwent conventional coronary angiography were evaluated with ECG-triggered thin section electron-beam CT with intravenous contrast enhancement. Multiplanar reformation of a stack of the images was performed to visualize coronary arteries. Two observers blind to the results of conventional coronary angiography independently evaluated the reformatted images. The sensitivity and specificity for the detection of significant lesions were 100 and 100% in the left main coronary artery, 83 and 84% in the left anterior descending artery, 67 and 96% in left circumflex artery, 63 and 79% in the right coronary artery, and 74 and 94% for total results, respectively. All false-positive results in the left anterior descending artery were caused by wall calcification, and in the right coronary artery, 83% of the false-positive results were caused by small slice gaps in noncalcified segments. Electron-beam CT was feasible for the detection of coronary artery stenoses. For interpretation of reformatted images, calcification and slice gaps should be taken into consideration.

Noninvasive definition of anatomic coronary artery disease by ultrafast computed tomographic scanning: A quantitative pathologic comparison study

Objectives. The aim of this study was to determine the relation between coronary artery calcification detected by ultrafast computed tomographic scanning and histopathologic coronary artery disease.Background. Recent studies suggest that discrete coronary artery calcification as visualized by ultrafast computed tomographic scanning may facilitate the noninvasive detection of estimation, or both, of the in situ extent of coronary disease. Such quantitative relations have not been established.Methods. Thirteen consecutive perfusion-fixed outopsy hearts (from eight male and five female patients aged 17 to 83 years) were scanned by ultrafast computed tomographic scanning in contiguous 3-mm tomographic sections. The major epicardial arteries were dissected free, positioned longitudinally and scanned again in cross section. Coronary artery calcification in a coronary segment was defined as the presence of one or more voxels with a computed tomographic density 130 Hounsfleld units. Each epicardial artery was sectioned longitudinally, stained and measured with a planimeter for quantification of cross-sectional and atherosclerotic plaque areas at 3-mm intervals, corresponding to the computed tomographic scans. A total of 522 paired coronary computed tomographic and histologic sections were studied.Results. Direct relations were found between ultrafast computed tomographic scanning coronary artery calcium burden and atherosclerotic plaque area and percent lumen area stenosis. However, the range for plaque area or percent lumen stenosis, or both, associated with a given calcium burden was broad. Three hundred thirty-one coronary segments showed no calcification by computed tomography. Although atherosclerotic disease was found in several corresponding pathologic specimens,97% of these noncalcified segments were associated with nonobstructive disease (<75% area stenosis); if no calcification was determined in an entire coronary vessel, all corresponding coronary disease was found to be nonobstructive. To determine the relation between arterial calcification and any atheromatous disease, computed tomographic calcium burden for each segment was paired with the histologic absence or presence of disease. Ultrafast computed tomographic scanning had a sensitivity and specificity of 59% and 90% and a negative and positive predictive value of 65% and 87%, respectively. A direct correlation was found (r = 0.99) between total calcium burden calculated from tomographic scans of the heart as a whole and scans of the arteries obtained in cross section.Conclusions. The detection of coronary calcification by ultrafast computed tomographic scanning is highly predictive of the presence of histopathologic coronary disease, but the use of this technique to define the extent of coronary disease may be limited. However, the absence of coronary calcification at any site is highly specific for the absence of obstructive disease.

Responses of atherosclerotic aorta to argon laser.

Lasers have been advocated to resect atherosclerotic plaques in the cardiovascular system, yet little information is available regarding the effects of laser on the range of occlusive lesions seen in the peripheral arterial tree. This study was conducted to assess the risk of perforation in human cadaveric aorta involved with variable degrees of atherosclerosis. Ten fresh segments of atherosclerotic human aorta were graded for extent of atherosclerosis, then subjected to argon laser energy within 48 hours. Using air as the conduction medium and with the fiber tip 2 or 5 mm from the vessel wall, the argon laser was applied to matched calcified and non-calcified arteries at 3.0-7.0 W and 10.0-13.5 W with energy density identical for matched pairs. Results were compared among segments which were normal in appearance or had only fatty streaks grossly with those with gross regional wall calcification. The mean penetration time (T) for calcified and non-calcified lesions at low and high power outputs was compared. (table; see text) Mean time to perforation and range of time necessary to produce perforation were greater in calcified than non-calcified segments at all power levels employed. These data suggest that atherosclerotic lesions vary in their response to argon laser. The presence of calcium may preclude resection of some plaques and protect against wall perforation.