Andrew P. Klein

Clinical Feasibility of a Fully Automated 3D Reconstruction of Rotational Coronary X-Ray Angiograms

Background—Although fixed view x-ray angiography remains the primary technique for anatomic imaging of coronary artery disease, the known shortcomings of 2D projection imaging may limit accurate 3D vessel and lesion definition and characterization. A recently developed method to create 3D images of the coronary arteries uses x-ray projection images acquired during a 180° C-arm rotation and continuous contrast injection followed by ECG-gated iterative reconstruction. This method shows promise for providing high-quality 3D reconstructions of the coronary arteries with no user interaction but requires clinical evaluation. Methods and Results—The reconstruction strategy was evaluated by comparing the reconstructed 3D volumetric images with the 2D angiographic projection images from the same 23 patients to ascertain overall image quality, lesion visibility, and a comparison of 3D quantitative coronary analysis with 2D quantitative coronary analysis. The majority of the resulting 3D volume images were rated as having high image quality (66%) and provided the physician with additional clinical information such as complete visualization of bifurcations and unobtainable views of the coronary tree. True-positive lesion detection rates were high (90 to 100%), whereas false-positive detection rates were low (0 to 8.1%). Finally, 3D quantitative coronary analysis showed significant similarity with 2D quantitative coronary analysis in terms of lumen diameters and provided vessel segment length free from the errors of foreshortening. Conclusions—Fully automated reconstruction of rotational coronary x-ray angiograms is feasible, produces 3D volumetric images that overcome some of the limitations of standard 2D angiography, and is ready for further implementation and study in the clinical environment.

Minimum Set of Cytochromes P450 for Reconstituting the Biosynthesis of Camalexin, a Major Arabidopsis Antibiotic

Bringing it all together: The missing key step in the biosynthesis of camalexin was uncovered by in vitro biochemical characterization. The coupling of Trp- and Cys-derived fragments through CS bond formation is promoted by an unusual cytochrome P450 CYP71A13. The in vitro reconstitution of the camalexin biosynthesis (left) from Trp and Cys was achieved using just three cytochromes P450. IAN=indole-3-acetonitrile.

Accelerated Solvent Extraction of Lignin from Aleurites moluccana (Candlenut) Nutshells

Lignin from candlenut shells was isolated using an ethanol-water accelerated solvent extraction method. Yields (based on Klason lignin) increased from about 14 to 33% as temperature increased from 100 to 195 °C and were also influenced by the amount of aqueous acid used to precipitate lignin from the extraction liquor. These yields were higher than could be obtained using a conventional dioxane-water acidolysis method. The resulting lignin was characterized by IR, 31P NMR, and 1H-13C HMQC NMR spectroscopic techniques. The lignin contained predominantly guaiacyl units, and both the total hydroxyl group content and phenolic hydroxyl group content were high.

Intervertebral disc height loss demonstrates the threshold of major pathological changes during degeneration

PurposeQuantitative MRI techniques were utilized to study intervertebral disc degeneration. Main focus was to develop a novel approach to quantify disc height loss associated with disc degeneration. Currently there is no universally accepted metric of degeneration based on measurement of disc height. Such quantitative imaging methods would complement qualitative visual assessment methods currently used and offer a valuable diagnostic tool.Methods51 adult participants took part in this MRI study. T2 weighted images were used to obtain disc height index (DHI) and also a semi-quantitative metric based on relative voxel intensities. For DHI, each disc was given a score based on standard deviations from the mean DHI of healthy discs. Diffusion Weighted MRI was used to assess morphological changes in the nucleus pulposus. Conventional Pfirrmann classification was used as the gold standard to assess these quantitative approaches.ResultsAt deviations of up to 1.5σ below normative disc height, levels of apparent diffusion coefficient (ADC) and normalized T2 intensity were maintained. Once disc compression reached 1.5σ, there was a massive drop in ADC and normalized T2 intensity. Pfirrmann degeneration scores also increased after the 1.5σ mark.ConclusionsThis study provides new, unbiased quantitative imaging tools to assess disc degeneration. We observed that these quantitative MRI measures indicate a threshold beyond which major pathological changes take place concurrently. Combined information from DHI, ADC and T2 images construct a set of novel biomarkers that could be used to identify degenerating discs that are approaching the threshold and possibly intervene before major pathologic changes occur.

Changes in perfusion and diffusion in the endplate regions of degenerating intervertebral discs: a DCE-MRI study

PurposeDynamic contrast-enhanced MRI (DCE-MRI) was used to investigate the associations between intervertebral disc degeneration and changes in perfusion and diffusion in the disc endplates.Methods56 participants underwent MRI scans. Changes in DCE-MRI signal enhancement in the endplate regions were analyzed. Also, a group template was generated for the endplates and enhancement maps were registered to this template for group analysis.ResultsDCE-MRI enhancement changed significantly in cranial endplates with increased degeneration. A similar trend was observed for caudal endplates, but it was not significant. Group-averaged enhancement maps revealed major changes in spatial distribution of endplate perfusion and diffusion with increasing disc degeneration especially in peripheral endplate regions.ConclusionsIncreased enhancement in the endplate regions of degenerating discs might be an indication of ongoing damage in these tissues. Therefore, DCE-MRI could aid in understanding the pathophysiology of disc degeneration. Moreover, it could be used in the planning of novel treatments such as stem cell therapy.

Biosynthesis of cabbage phytoalexins from indole glucosinolate

Significance Cruciferous vegetables—such as broccoli, mustard greens, and turnip—produce a variety of indole- and sulfur-containing chemicals when attacked by pathogens. These compounds, termed phytoalexins, are thought to serve as an important defense mechanism for the plant. Several phytoalexins have been shown to also have anticancer properties, raising the possibility that dietary exposure may be important to human health. Here, we report a minimal set of enzymes required to make brassinin, the parent cruciferous phytoalexin, from the well-studied glucosinolates. These genes enabled production of brassinin and related phytoalexins in tobacco leaves at levels comparable to those measured in cruciferous vegetables. The complete biosynthetic pathway to brassinin is critical for using metabolic engineering to characterize the biological role of indole–sulfur phytoalexins. Brassica crop species are prolific producers of indole–sulfur phytoalexins that are thought to have an important role in plant disease resistance. These molecules are conspicuously absent in the model plant Arabidopsis thaliana, and little is known about the enzymatic steps that assemble the key precursor brassinin. Here, we report the minimum set of biosynthetic genes required to generate cruciferous phytoalexins starting from the well-studied glucosinolate pathway. In vitro biochemical characterization revealed an additional role for the previously described carbon–sulfur lyase SUR1 in processing cysteine–isothiocyanate conjugates, as well as the S-methyltransferase DTCMT that methylates the resulting dithiocarbamate, together completing a pathway to brassinin. Additionally, the β-glucosidase BABG that is present in Brassica rapa but absent in Arabidopsis was shown to act as a myrosinase and may be a determinant of plants that synthesize phytoalexins from indole glucosinolate. Transient expression of the entire pathway in Nicotiana benthamiana yields brassinin, demonstrating that the biosynthesis of indole–sulfur phytoalexins can be engineered into noncruciferous plants. The identification of these biosynthetic enzymes and the heterologous reconstitution of the indole–sulfur phytoalexin pathway sheds light on an important pathway in an edible plant and opens the door to using metabolic engineering to systematically quantify the impact of cruciferous phytoalexins on plant disease resistance and human health.

Enhanced stent visualization: A case series demonstrating practical applications during PCI

BACKGROUND Visualization of coronary stents is increasingly challenging due to the reduction in stent strut thickness to improve deliverability. On the other hand stent expansion and precise implantation in the target vessel are important in optimizing short and long-term outcomes of stent-based revascularization. Stentboost Subtract is a novel X-ray technique that improves visualization of deployed stents in the coronary arteries. Using motion compensation and integration of multiple non-contrast projection images from a fixed gantry position, this new technique depicts stent morphology allowing assessment of stent expansion and extent of overlap with adjacent stents. We present a case series in which enhanced stent visualization (ESV) facilitated interventions. METHODS The clinical and angiographic characteristics of 6 cases utilizing ESV were reviewed. All ESV acquisitions in this case series utilized an 8 in. field of view (FOV), 3 ml/sec. for a total of 6 ml of contrast, and placement of balloon markers in the region of interest. RESULTS The cases presented significantly facilitated the identification of bifurcation stenting techniques, precise stent positioning, stent underexpansion and assisted with defining stent-vessel wall relationship that was additive to intravascular ultrasound. CONCLUSIONS ESV is a novel tool used in coronary interventions that facilitates non-invasive assessment of stent positioning, expansion and stent-vessel interactions. This inexpensive ESV technique is complimentary to IVUS and in some cases obviates its need.

Two cytochromes P450 catalyze S-heterocyclizations in cabbage phytoalexin biosynthesis

Phytoalexins are abundant in edible crucifers and have important biological activities, yet no dedicated gene for their biosynthesis is known. Here, we report two new cytochromes P450 from Brassica rapa (Chinese cabbage) that catalyze unprecedented S-heterocyclizations in cyclobrassinin and spirobrassinin biosynthesis. Our results reveal the first genetic and biochemical insights into the biosynthesis of a prominent pair of dietary metabolites, and have implications for pathway discovery across >20 recently sequenced crucifers.

Rotational Coronary Angiography

The numerous well-documented limitations of standard fixed-acquisition coronary angiography led to the development of rotational angiography. This acquisition method uses automated gantry movements while numerous angiographic projections are obtained, and thus overcomes many of the limitations of standard angiography. This article highlights the techniques, advantages, and disadvantages of each type of rotational angiography currently commercially available. Also included is a discussion of the evolution of rotational angiography, from its initial conception and pilot studies to its latest step forward on the developmental road towards enhanced coronary imaging.

Preoperative Diffusion Tensor Imaging: Improving Neurosurgical Outcomes in Brain Tumor Patients

Preoperative mapping has revolutionized neurosurgical care for brain tumor patients. Maximizing resections has improved diagnosis, optimized treatment algorithms, and decreased potentially devastating postoperative deficits. Although mapping has multiple steps and complimentary localization sources, diffusion tensor imaging (DTI) excels in its essential role in depicting white matter tracts. A thorough understanding of DTI, data visualization methods, and limitations with mastery of functional and dysfunctional white matter anatomy is necessary to realize the potential of DTI. By establishing spatial relationships between lesion borders and functional networks preoperatively and intraoperatively, DTI is central to high-risk neurosurgical resections and becoming the standard of care.