Fully automated segmentation and tracking of the intima media thickness in ultrasound video sequences of the common carotid artery

Abstract—The robust identification and measurement of the intima media thickness (IMT) has a high clinical relevance because it represents one of the most precise predictors used in the assessment of potential future cardiovascular events. To facilitate the analysis of arterial wall thickening in serial clinical investigations, in this paper we have developed a novel fully automatic algorithm for the segmentation, measurement, and tracking of the intima media complex (IMC) in B-mode ultrasound video sequences. The proposed algorithm entails a two-stage image analysis process that initially addresses the segmentation of the IMC in the first frame of the ultrasound video sequence using a model-based approach; in the second step, a novel customized tracking procedure is applied to robustly detect the IMC in the subsequent frames. For the video tracking procedure, we introduce a spatially coherent algorithm called adaptive normalized correlation that prevents the tracking process from converging to wrong arterial interfaces. This represents the main contribution of this paper and was developed to deal with inconsistencies in the appearance of the IMC over the cardiac cycle. The quantitative evaluation has been carried out on 40 ultrasound video sequences of the common carotid artery (CCA) by comparing the results returned by the developed algorithm with respect to ground truth data that has been manually annotated by clinical experts. The measured IMTmean ± standard deviation recorded by the proposed algorithm is 0.60 mm ± 0.10, with a mean coefficient of variation (CV) of 2.05%, whereas the corresponding result obtained for the manually annotated ground truth data is 0.60 mm ± 0.11 with a mean CV equal to 5.60%. The numerical results reported in this paper indicate that the proposed algorithm is able to correctly segment and track the IMC in ultrasound CCA video sequences, and we were encouraged by the stability of our technique when applied to data captured under different imaging conditions. Future clinical studies will focus on the evaluation of patients that are affected by advanced cardiovascular conditions such as focal thickening and arterial plaques

Genome wide association study of nonsynonymous Single Nucleotide Polymorphisms for seven common diseases

Background: Associations of several Single Nucleotide Polymorphisms (SNPs) with common diseases like Coronary Artery Disease (CAD), Crohn’s Disease (CD), Hypertension (HT), Bipolar Disorder (BD), Type 1 Diabetes (T1D), Type 2 Diabetes (T2D) and Rheumatoid Arthritis (RA) were identified in a study conducted by the Wellcome Trust Case Control Consortium (WTCCC) (1). WTCCC study compared the effects of genetic variations in 14,000 cases and 3000 shared controls and identified 24 independent associations with the diseases mentioned above using the genotype information of approximately 500,000 directly genotyped SNPs and genotype information simulated at 2.8 million loci studied by the International Hapmap Project(2). We hypothesize that there are more chances of finding association of rare SNPs with diseases by refined analysis of non-synonymous SNPs (nsSNPs) in genome wide association studies. In the present study we analyzed the association of 12,660 nsSNPs using a case control study in the WTCCC population. Materials and methods: We simulated the genotypes at 10,798 nsSNP loci studied by the Stage 2 HapMap project using the genotype information from WTCCC for all 14,000 individuals studied for seven diseases and in 3000 controls. These simulations were done using the genetic recombination map of the respective regions obtained from the haplotypes of Hapmap European population. We performed these simulations or imputations using two widely used programs called IMPUTE(3) and MACH. All the genotyped SNPs used to impute missing genotypes passed quality control tests for Hardy Weinberg equilibrium (p\u3c10-2), Minor allele frequency (MAF\u3c10-2), missing genotypes per marker (more than 10%) performed using programs in PLINK genome wide analysis package. Subsequent case control association of 10,798 imputed nsSNPs and 1,862 genotyped nsSNPs was performed using an additive model and genotype model in a frequentist and bayesian framework. Results: We found 2 nsSNPs associated with BD, 2 with Coronary Artery Disease, 7 with CD, 1 with HT, 22 with RA, 17 with T1D and 2 with T2D. In total, 53 new associations with the seven diseases (p \u3c 5 x 10-6) studied by WTCCC. We also developed a pipeline which summarizes quality control measures which should be considered to minimize false associations in genome wide association studies. In any such large scale genome wide association studies, there are chances of getting false positives which show association at loci imputed using genetic information from Hapmap. This can arise due to the genotype quality of tag SNPs which are in high linkage disequilibrium (LD) in the region where the missing genotype is simulated. Such false associations can be ruled out by visually inspecting the cluster plots of genotyped SNPs which are in high LD in respective regions. A comprehensive quality control will be performed at this stage by visually inspecting cluster plots of all genotyped SNPs which are in high LD with the imputed SNPs associated with each disease which will count out any such influences on new associations identified in our study

Recurring themes arising during medical research ethics committee review.

A standard application form for the ethical review of health-related research studies has recently been adopted by many Irish medical research ethics committees. In order to assess the impact of the new form, we reviewed all comments made by the Beaumont Hospital Ethics Committee during two six-month periods, immediately prior to adoption of the new form (2010), and soon afterwards (2011). Neither volume nor comment type differed significantly between the two observation periods. Participant documentation (information leaflets and consent forms) accounted for the largest proportion of comments (2010; 44%, 2011; 37%). Other common areas prompting queries were study administration (7%), design (12%) and procedures (13%), participant selection and recruitmen (8%), and lastly data protection (9%). Because of these findings, the standard operating procedures of the committee have been revised--use of provided template participant documentation is strongly encouraged, and a \u22Recurring Review Themes\u22 checklist is highlighted to all applicants

An automatic 2D CAD algorithm for the segmentation of the IMT in ultrasound carotid artery images

Common carotid intima-media thickness (IMT) is a reliable measure of early atherosclerosis - its accurate measurement can be used in the process of evaluating the presence and tracking the progression of disease. The aim of this study is to introduce a novel unsupervised Computer Aided Detection (CAD) algorithm that is able to identify and measure the IMT in 2D ultrasound carotid images. The developed technique relies on a suite of image processing algorithms that embeds a statistical model to identify the two interfaces that form the IMT without any user intervention. The proposed image segmentation scheme is based on a spatially continuous vascular model and consists of several steps including data preprocessing, edge filtering, model selection, edge reconstruction and data refinement. To conduct a quantitative evaluation each image was manually segmented by clinical experts and performance metrics between the segmentation results obtained by the proposed method and the ground truth data were calculated. The experimental results show that the proposed CAD system is robust in accurately estimating the IMT in ultrasound carotid data

P-67: Dose response antihypertensive efficacy of aliskiren (SPP 100), an orally active renin inhibitor

Aliskiren (SPP 100), an orally active renin inhibitor, has been shown to inhibit the production of angiotensin I and angiotensin II in healthy volunteers. In a pilot study, aliskiren decreased BP in hypertensive patients at daily doses of 75 and 150 mg. In this multi-centre, double-blind, active comparator trial, the dose-dependent effects of aliskiren were evaluated in 226 patients with mild to moderate hypertension. Parallel groups of randomized patients were assessed at the end of a washout period and again after a 4-week treatment period. Treatment consisted of single oral daily doses of aliskiren (37.5, 75, 150 or 300 mg) or of losartan 100 mg once daily. Daytime ambulatory systolic BP was defined as the primary variable of the study. As illustrated in the figure, a clear dose-response curve was observed for the decrease (mean +/- SEM) in daytime ambulatory systolic BP. The mean (SD) change at the end of the 4-week treatment period was -1.3 (9.5) mmHg, -5.5 (10.6) mmHg, -8.5 (10.4) mmHg, -10.5 (10.7) mmHg, and -11.1 (13.4) mmHg for 37.5, 75, 150, and 300 mg aliskiren and 100mg losartan, respectively. Statistically significant lowering occurred with 75, 150 and 300 mg of aliskiren. The daytime ambulatory systolic BP responses to aliskiren doses of 150 and 300 mg were not significantly different from that of 100 mg losartan. Similar results were shown for daytime ambulatory diastolic BP and for night-time ambulatory systolic and diastolic BP. Aliskiren was well tolerated - there was no increase in the number of adverse events with increasing doses of aliskiren, and the safety profile of aliskiren was similar to that of losartan. The results of this dose-ranging study confirm a dose-dependent reduction in BP with aliskiren in mild to moderate hypertension. Additional exploratory studies testing the efficacy and safety of this new renin inhibitor in patients with renal disease and congestive heart failure are currently underwa

A polymorphism in ACE2 is associated with a lower risk for fatal cardiovascular events in females: the MORGAM project

Angiotensin II, a vasoconstrictor and the main effector molecule of the renin-angiotensin system, is known to influence inflammation, thrombosis, low-density lipoprotein oxidation and growth factors, all of which contribute to cardiovascular disease. The associations of polymorphisms in the angiotensin-converting enzyme 2 (ACE2) gene with cardiovascular risk have not been fully determined. Single nucleotide polymorphisms (SNPs) in ACE2 were genotyped in participants of the prospective MORGAM study (n = 5092) from five cohorts: ATBC, FINRISK, Northern Sweden, PRIME/Belfast and PRIME/France. Using a case-cohort design, associations were sought between SNPs and haplotypes with cardiovascular events during follow-up (Cox proportional hazards model). The comparison group were a subset of all MORGAM participants who were selected to ensure similar age and sex distributions among the cases and controls. The A allele of the rs2285666 SNP (HR = 0.3, p = 0.04) was significantly associated with the risk of cardiovascular death in female subjects. These findings complement those found in other studies of SNPs in the ACE2 gene in relation to cardiovascular disease risk. As females carry two copies of the ACE2 gene, and given its plausible biological role in cardiovascular disease risk, further studies of ACE2 should be prioritized

Polymorphisms of the Flavin containing monooxygenase 3 (FMO3) gene do not predispose to essential hypertension in Caucasians.

BACKGROUND: The recessive disorder trimethylaminuria is caused by defects in the FMO3 gene, and may be associated with hypertension. We investigated whether common polymorphisms of the FMO3 gene confer an increased risk for elevated blood pressure and/or essential hypertension. METHODS: FMO3 genotypes (E158K, V257M, E308G) were determined in 387 healthy subjects with ambulatory systolic and diastolic blood pressure measurements, and in a cardiovascular disease population of 1649 individuals, 691(41.9%) of whom had a history of hypertension requiring drug treatment. Haplotypes were determined and their distribution noted. RESULTS: There was no statistically significant association found between any of the 4 common haplotypes and daytime systolic blood pressure in the healthy population (p = 0.65). Neither was a statistically significant association found between the 4 common haplotypes and hypertension status among the cardiovascular disease patients (p = 0.80). CONCLUSION: These results suggest that the variants in the FMO3 gene do not predispose to essential hypertension in this population

Human cytomegalovirus protein pUL36: A dual cell death pathway inhibitor.

Human cytomegalovirus (HCMV) is an important human pathogen and a paradigm of intrinsic, innate, and adaptive viral immune evasion. Here, we employed multiplexed tandem mass tag-based proteomics to characterize host proteins targeted for degradation late during HCMV infection. This approach revealed that mixed lineage kinase domain-like protein (MLKL), a key terminal mediator of cellular necroptosis, was rapidly and persistently degraded by the minimally passaged HCMV strain Merlin but not the extensively passaged strain AD169. The strain Merlin viral inhibitor of apoptosis pUL36 was necessary and sufficient both to degrade MLKL and to inhibit necroptosis. Furthermore, mutation of pUL36 Cys131 abrogated MLKL degradation and restored necroptosis. As the same residue is also required for pUL36-mediated inhibition of apoptosis by preventing proteolytic activation of procaspase-8, we define pUL36 as a multifunctional inhibitor of both apoptotic and necroptotic cell death

Effect of Arteriovenous Anastomosis on Blood Pressure Reduction in Patients With Isolated Systolic Hypertension Compared With Combined Hypertension

Background: Options for interventional therapy to lower blood pressure (BP) in patients with treatment‐resistant hypertension include renal denervation and the creation of an arteriovenous anastomosis using the ROX coupler. It has been shown that BP response after renal denervation is greater in patients with combined hypertension (CH) than in patients with isolated systolic hypertension (ISH). We analyzed the effect of ROX coupler implantation in patients with CH as compared with ISH. Methods and Results: The randomized, controlled, prospective ROX Control Hypertension Study included patients with true treatment‐resistant hypertension (office systolic BP ≥140 mm Hg, average daytime ambulatory BP ≥135/85 mm Hg, and treatment with ≥3 antihypertensive drugs including a diuretic). In a post hoc analysis, we stratified patients with CH (n=31) and ISH (n=11). Baseline office systolic BP (177±18 mm Hg versus 169±17 mm Hg, P=0.163) and 24‐hour ambulatory systolic BP (159±16 mm Hg versus 154±11 mm Hg, P=0.463) did not differ between patients with CH and those with ISH. ROX coupler implementation resulted in a significant reduction in office systolic BP (CH: −29±21 mm Hg versus ISH: −22±31 mm Hg, P=0.445) and 24‐hour ambulatory systolic BP (CH: −14±20 mm Hg versus ISH: −13±15 mm Hg, P=0.672), without significant differences between the two groups. The responder rate (office systolic BP reduction ≥10 mm Hg) after 6 months was not different (CH: 81% versus ISH: 82%, P=0.932). Conclusions: Our data suggest that creation of an arteriovenous anastomosis using the ROX coupler system leads to a similar reduction of office and 24‐hour ambulatory systolic BP in patients with combined and isolated systolic hypertension. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01642498

Fistula awareness among sisters of women with fistula

ObjectiveTo determine whether sisters of women with obstetric fistula (OF) were aware of their sisters’ condition, in order to inform the development of survey questions that adapt the sister‐based method to fistula rate estimation.MethodsTwelve women with OF and 20 of their sisters were interviewed using semi‐structured questionnaires in rural Uganda in 2007. Topics included fistula awareness and perceptions of causality.ResultsEleven women had vesicovaginal fistula and 1 had rectovaginal fistula. Three were primiparous at time of fistula occurrence; 6 had a parity of 6 or more. Nineteen sisters were aware their sister had OF; 12 became aware at the time of occurrence. The majority of participants (fistula patients and their sisters) associated OF with mistakes made by hospital personnel or problems during procedures.ConclusionSisters were generally aware of OF within their family. Larger studies are needed to assess the validity and reliability of the sister‐based method in capturing fistula through household surveys. In the present study, there was a widespread perception among fistula patients and their sisters that fistula is caused by medical procedures. More research is needed to understand this perception, and program development efforts are required to improve patient perceptions of hospital care.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135323/1/ijgo232.pd