Influence of shape-memory stent grafts on local aortic compliance

The effect of repair techniques on the biomechanics of the aorta is poorly understood, resulting in significant levels of postoperative complications for patients worldwide. This study presents a computational analysis of the influence of Nitinol-based devices on the biomechanical performance of a healthy patient-specific human aorta. Simulations reveal that Nitinol stent-grafts stretch the artery wall so that collagen is stretched to a straightened high-stiffness configuration. The high-compliance regime (HCR) associated with low diastolic lumen pressure is eliminated, and the artery operates in a low-compliance regime (LCR) throughout the entire cardiac cycle. The slope of the lumen pressure–area curve for the LCR post-implantation is almost identical to that of the native vessel during systole. This negligible change from the native LCR slope occurs because the stent-graft increases its diameter from the crimped configuration during deployment so that it reaches a low-stiffness unloading plateau. The effective radial stiffness of the implant along this unloading plateau is negligible compared to the stiffness of the artery wall. Provided the Nitinol device unloads sufficiently during deployment to the unloading plateau, the degree of oversizing has a negligible effect on the pressure–area response of the vessel, as each device exerts approximately the same radial force, the slope of which is negligible compared to the LCR slope of the native artery. We show that 10% oversizing based on the observed diastolic diameter in the mid descending thoracic aorta results in a complete loss of contact between the device and the wall during systole, which could lead to an endoleak and stent migration. 20% oversizing reaches the Dacron enforced area limit (DEAL) during the pulse pressure and results in an effective zero-compliance in the later portion of systole.

     

Development and application of a multimodal contrast agent for SPECT/CT hybrid imaging

Hybrid or multimodality imaging is often applied in order to take advantage of the unique and complementary strengths of individual imaging modalities. This hybrid noninvasive imaging approach can provide critical information about anatomical structure in combination with physiological function or targeted molecular signals. While recent advances in software image fusion techniques and hybrid imaging systems have enabled efficient multimodal imaging, accessing the full potential of this technique requires development of a new toolbox of multimodal contrast agents that enhance the imaging process. Toward that goal, we report the development of a hybrid probe for both single photon emission computed tomography (SPECT) and X-ray computed tomography (CT) imaging that facilitates high-sensitivity SPECT and high spatial resolution CT imaging. In this work, we report the synthesis and evaluation of a novel intravascular, multimodal dendrimer-based contrast agent for use in preclinical SPECT/CT hybrid imaging systems. This multimodal agent offers a long intravascular residence time (t(1/2) = 43 min) and sufficient contrast-to-noise for effective serial intravascular and blood pool imaging with both SPECT and CT. The colocalization of the dendritic nuclear and X-ray contrasts offers the potential to facilitate image analysis and quantification by enabling correction for SPECT attenuation and partial volume errors at specified times with the higher resolution anatomic information provided by the circulating CT contrast. This may allow absolute quantification of intramyocardial blood volume and blood flow and may enable the ability to visualize active molecular targeting following clearance from the blood.     

The Wavelet-Based Cluster Analysis for Temporal Gene Expression Data

A variety of high-throughput methods have made it possible to generate detailed temporal expression data for a single gene or large numbers of genes. Common methods for analysis of these large data sets can be problematic. One challenge is the comparison of temporal expression data obtained from different growth conditions where the patterns of expression may be shifted in time. We propose the use of wavelet analysis to transform the data obtained under different growth conditions to permit comparison of expression patterns from experiments that have time shifts or delays. We demonstrate this approach using detailed temporal data for a single bacterial gene obtained under 72 different growth conditions. This general strategy can be applied in the analysis of data sets of thousands of genes under different conditions.[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]     

Validity of Antibodies in Lymphocyte Supernatant in Diagnosing Tuberculosis in Severely Malnourished Children Presenting with Pneumonia

BackgroundThe diagnosis of tuberculosis (TB) in young children can be challenging, especially in severely malnourished children. There is a critical need for improved diagnostics for children. Thus, we sought to evaluate the performance of a technique that measures antibodies in lymphocyte supernatant (ALS) for the diagnosis of TB in severely malnourished children presenting with suspected pneumonia.MethodsChildren less than 5 years with severe acute malnutrition and radiological features of pneumonia admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh, were enrolled consecutively following informed written consent. In addition to clinical and radiological assessment, samples taken for TB diagnosis included gastric lavage fluid and induced sputum for microbiological confirmation. ALS was measured from venous blood, and results were evaluated in children classified as “confirmed”, “non-confirmed TB” or “not TB”.ResultsAmong 224 children who had ALS analysis, 12 (5.4%) children had microbiologically “confirmed TB”, a further 41 (18%) had clinically diagnosed “non-confirmed TB” and the remaining 168 (75%) were considered not to have TB. ALS was positive in 89 (40%) and negative in 85 (39%) of children, with a large number (47 or 21%) reported as “borderline”. These proportions were similar between the three diagnostic groups. The sensitivity and specificity of ALS when comparing “Confirmed TB” to “Not TB” was only 67% (95% CI: 31–91%) and 51% (95% CI: 42–60%), respectively.

Conclusions and Significance

Our data suggest that ALS is not sufficiently accurate to improve the diagnosis of TB in children with severe malnutrition.     

Imaging angiogenesis

Angiogenesis represents the formation of new capillaries by cellular outgrowth from existing microvessels and plays a critical role in the response to ischemia associated with peripheral arterial disease and myocardial infarction. Imaging of angiogenesis would be valuable in risk stratification of patients with arterial occlusive disease. The progress in noninvasive imaging strategies to assess angiogenesis has been made possible with the availability of many technological advances, which include dedicated hybrid SPECT-CT and PET-CT systems and agents targeted at molecular markers of the angiogenic process, involving both receptor-probe interactions and reporter gene technology. These novel targeted approaches for imaging angiogenesis will complement standard imaging of physiological parameters and will play a crucial role for evaluation of therapeutic interventions to promote angiogenesis.     

ArchAlign: coordinate-free chromatin alignment reveals novel architectures

To facilitate identification and characterization of genomic functional elements, we have developed a chromatin architecture alignment algorithm (ArchAlign). ArchAlign identifies shared chromatin structural patterns from high-resolution chromatin structural datasets derived from next-generation sequencing or tiled microarray approaches for user defined regions of interest. We validated ArchAlign using well characterized functional elements, and used it to explore the chromatin structural architecture at CTCF binding sites in the human genome. ArchAlign is freely available at http://www.acsu.buffalo.edu/~mjbuck/ArchAlign.html.     

Targeted molecular imaging of angiogenesis in PET and SPECT: a review

Over the past few decades, there have been significant advancements in the imaging techniques of positron emission tomography (PET) and single photon emission tomography (SPECT). These changes have allowed for the targeted imaging of cellular processes and the development of hybrid imaging systems (e.g., SPECT/CT and PET/CT), which provide both functional and structural images of biological systems. One area that has garnered particular attention is angiogenesis as it relates to ischemic heart disease and limb ischemia. Though the aforementioned techniques have benefits and consequences, they enable scientists and clinicians to identify regions that are vulnerable to or have been exposed to ischemic injury via non-invasive means. This literature review highlights the advancements in molecular imaging techniques and specific probes as they pertain to the process of angiogenesis in cardiovascular disease.