2-D magnetic resonance spectroscopic imaging of the pediatric brain using compressed sensing.

BACKGROUND: Magnetic resonance spectroscopic imaging helps to determine abnormal brain tissue conditions by evaluating metabolite concentrations. Although a powerful technique, it is underutilized in routine clinical studies because of its long scan times. OBJECTIVE: In this study, we evaluated the feasibility of scan time reduction in metabolic imaging using compressed-sensing-based MR spectroscopic imaging in pediatric patients undergoing routine brain exams. MATERIALS AND METHODS: We retrospectively evaluated compressed-sensing reconstructions in MR spectroscopic imaging datasets from 20 pediatric patients (11 males, 9 females; average age: 5.4±4.5 years; age range: 3 days to 16 years). We performed retrospective under-sampling of the MR spectroscopic imaging datasets to simulate accelerations of 2-, 3-, 4-, 5-, 7- and 10-fold, with subsequent reconstructions in MATLAB. Metabolite maps of N-acetylaspartate, creatine, choline and lactate (where applicable) were quantitatively evaluated in terms of the root-mean-square error (RMSE), peak amplitudes and total scan time. We used the two-tailed paired t-test along with linear regression analysis to statistically compare the compressed-sensing reconstructions at each acceleration with the fully sampled reference dataset. RESULTS: High fidelity was maintained in the compressed-sensing MR spectroscopic imaging reconstructions from 50% to 80% under-sampling, with the RMSE not exceeding 3% in any dataset. Metabolite intensities and ratios evaluated on a voxel-by-voxel basis showed no statistically significant differences and mean metabolite intensities showed high correlation compared to the fully sampled reference dataset up to an acceleration factor of 5. CONCLUSION: Compressed-sensing MR spectroscopic imaging has the potential to reduce MR spectroscopic imaging scan times for pediatric patients, with negligible information loss.

Fast data acquisition techniques in magnetic resonance spectroscopic imaging.

Magnetic resonance spectroscopic imaging (MRSI) is an important technique for assessing the spatial variation of metabolites in vivo. The long scan times in MRSI limit clinical applicability due to patient discomfort, increased costs, motion artifacts, and limited protocol flexibility. Faster acquisition strategies can address these limitations and could potentially facilitate increased adoption of MRSI into routine clinical protocols with minimal addition to the current anatomical and functional acquisition protocols in terms of imaging time. Not surprisingly, a lot of effort has been devoted to the development of faster MRSI techniques that aim to capture the same underlying metabolic information (relative metabolite peak areas and spatial distribution) as obtained by conventional MRSI, in greatly reduced time. The gain in imaging time results, in some cases, in a loss of signal-to-noise ratio and/or in spatial and spectral blurring. This review examines the current techniques and advances in fast MRSI in two and three spatial dimensions and their applications. This review categorizes the acceleration techniques according to their strategy for acquisition of the k-space. Techniques such as fast/turbo-spin echo MRSI, echo-planar spectroscopic imaging, and non-Cartesian MRSI effectively cover the full k-space in a more efficient manner per TR . On the other hand, techniques such as parallel imaging and compressed sensing acquire fewer k-space points and employ advanced reconstruction algorithms to recreate the spatial-spectral information, which maintains statistical fidelity in test conditions (ie no statistically significant differences on voxel-wise comparisions) with the fully sampled data. The advantages and limitations of each state-of-the-art technique are reviewed in detail, concluding with a note on future directions and challenges in the field of fast spectroscopic imaging.

Anatomy and Surgical Approaches to the Rabbit Nasal Septum.

IMPORTANCE: The rabbit is the primary animal model used to investigate aspects of nasal surgery. Although several studies have used this model, none has provided a comprehensive analysis of the surgical anatomy and techniques used to gain access to the rabbit nasal fossae and septum. OBJECTIVE: To describe and optimize the surgical anatomy and approach to the rabbit nasal vault and septal cartilage. DESIGN, SETTING, AND PARTICIPANTS: In an ex vivo animal study conducted at an academic medical center, preliminary cadaveric dissections were performed on rabbit head specimens to establish familiarity with relevant anatomy and rehearse various approaches. Live Pasteurella-free New Zealand white rabbits (3.5-4.0 kg) were used to further develop this surgical technique developed here. Access of the nasal vault was gained through a midline nasal dorsum incision and creation of an osteoplastic flap with a drill. Submucosal resection was performed with preservation of the mucoperichondrium. All rabbits were monitored daily for 4 weeks in the postoperative period for signs of infection, pain, and complications. The study was conducted from June 1, 2014, to December 1, 2014. MAIN OUTCOMES AND MEASURES: Surgical anatomy and techniques used to gain access to the rabbit nasal vault and harvest septal cartilage. RESULTS: Four Pasteurella-free New Zealand white rabbits (Western Organ Rabbit Co), ranging in age from 9 to 12 months and weighing between 3.5 and 4.0 kg, were used in this study. Initial dissections demonstrated the feasibility of harvesting septal cartilage while preserving the mucoperichondrial envelope. Access to the nasal vault through this 3-osteotomy approach allowed for maximal exposure to the nasal cavity bilaterally while maintaining the integrity of the mucoperichondrium following septal cartilage harvest. The maximum amount of bulk, en bloc, cartilage harvested was 1.0 × 2.5 cm. Following surgical dissection, all animals maintained adequate airway patency and support to midface structures. Furthermore, all specimens preserved the integrity of the mucoperichondrium, septum, vascular anatomy, and airway dynamics. No operative complications, postoperative airway compromise, or infections were observed. CONCLUSIONS AND RELEVANCE: Access to the rabbit nasal vault and septal cartilage is feasible through a variety of surgical approaches and techniques. To date, this is the first study to meticulously document and review the surgical approaches to the rabbit nasal cavity. This approach describes a novel, 3-osteotomy method of accessing the nasal cavity bilaterally and successfully harvesting rabbit septal cartilage in a submucoperichondrial plane. The ability to preserve native anatomy and function allows for improved outcomes in translational and animal guided clinical research. LEVEL OF EVIDENCE: NA.

Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for a multitude of reasons including very late diagnosis. This in part is due to the lack of understanding of the biological behavior of PDAC and the ineffective screening for this disease. Significant efforts have been dedicated to finding the appropriate serum and imaging biomarkers to help early detection and predict response to treatment of PDAC. Carbohydrate antigen 19-9 (CA 19-9) has been the most validated serum marker and has the highest positive predictive value as a stand-alone marker. When combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA 125), CA 19-9 can help predict the outcome of patients to surgery and chemotherapy. A slew of novel serum markers including multimarker panels as well as genetic and epigenetic materials have potential for early detection of pancreatic cancer, although these remain to be validated in larger trials. Imaging studies may not correlate with elevated serum markers. Critical features for determining PDAC include the presence of a mass, dilated pancreatic duct, and a duct cut-off sign. Features that are indicative of early metastasis includes neurovascular bundle involvement, duodenal invasion, and greater post contrast enhancement. 18-F-fluorodeoxyglucose (18-FDG) radiotracer uptake and changes following treatment may predict patient overall survival following treatment. Similarly, pretreatment apparent diffusion coefficient (ADC) values may predict prognosis with lower ADC lesions having worse outcome. Although these markers have provided significant improvement in the care of pancreatic cancer patients, further advancements can be made with perhaps better combination of markers or discovery of unique marker(s) to pancreatic cancer.

Neuronal network structuring induces greater neuronal activity through enhanced astroglial development.

The confluence of micropatterning, microfabricated multielectrode arrays, and low-density neuronal culture techniques make possible the growth of patterned neuronal circuits overlying multielectrode arrays. Previous studies have shown synaptic interaction within patterned cultures which was more active on average than random cultures. In our present study, we found patterned cultures to have up to five times more astrocytes and three times more neurons than random cultures. In addition, faster development of synapses is also seen in patterned cultures. Together, this yielded greater overall neuronal activity as evaluated by the number of active electrodes. Our finding of astrocytic proliferation within serum-free culture is also novel.

Long-term in vivo stability of rabbit nasal septal cartilage following laser cartilage reshaping: a pilot investigation.

BACKGROUND AND OBJECTIVES: To evaluate the long-term effect of laser cartilage reshaping on rabbit nasal septal cartilage viability and mechanical integrity in an in vivo model. STUDY DESIGN/MATERIALS AND METHODS: In vivo animal investigation. Rabbit septal cartilage specimens were laser (Nd:YAG, lambda = 1.32 mum, spot size 5.4-mm diameter, 10 W, 10 seconds, 50 Hz PPR) reshaped and subsequently reimplanted into an interscapular subcutaneous pocket. Specimens were harvested at 8 and 12 months and evaluated using photography, flow cytometry, and histology. RESULTS: Grossly, specimens showed alteration in the physical integrity with varying degrees of tissue resorption. The non-irradiated control specimens demonstrated significantly increased stiffness. Histologically, there was marked depletion of the extracellular matrix and an overall reduction in tissue mass in laser irradiated tissues. However, flow cytometry data identified viable chondrocytes in laser-irradiated specimens that were identical to those observed in controls. CONCLUSIONS: Study results demonstrate that the rabbit nasal septal cartilage model can be effectively used to study laser reshaping, however alternative recipient sites with perichondrial lining, such as the pinna, may provide a more realistic physiologic environment for reshaped graft tissue. The dosimetry used in this pilot study likely led to significant thermal injury. Study results underscore the importance of elucidating the optimal laser dosimetry required to initiate permanent shape change while minimizing thermal damage.

Gold-coated microelectrode array with thiol linked self-assembled monolayers for engineering neuronal cultures.

We report the use of a gold coating on microelectrode arrays (MEAs) to enable the use of the relatively reliable surface modification chemistry afforded by alkanethiol self-assembled monolayers (SAMs). The concept is simple and begins with planar MEAs, which are commercially available for neuronal cell culture and for brain slice studies. A gold film, with an intermediate adhesive layer of titanium, is deposited over the insulation of an existing MEA in a manner so as to be thin enough for transmission light microscopy as well as to avoid electrical contact to the electrodes. The alkanethiol-based linking chemistry is then applied for the desired experimental purpose. Here we show that polylysine linked to alkanethiol SAM can control the geometry of an in vitro hippocampal neuronal network grown on the MEA. Furthermore, recordings of neuronal action potentials from random and patterned networks suggest that the gold coating does not significantly alter the electrode properties. This design scheme may be useful for increasing the number of neurons located in close proximity to the electrodes. Realization of in vitro neuronal circuits on MEAs may significantly benefit basic neuroscience studies, as well as provide the insight relevant to applications such as neural prostheses or cell-based biosensors. The gold coating technique makes it possible to use the rich set of thiol-based surface modification techniques in combination with MEA recording.

A modified microstamping technique enhances polylysine transfer and neuronal cell patterning.

Macromolecular microstamping with polydimethylsiloxane (PDMS) stamps has been demonstrated to transfer proteins onto glassy substrates for antigen or antibody detection and for cell patterning. For many applications, including neuronal cell patterning, it is important to assure reliable transfer of sufficient quantity of protein. Research has shown that protein transfer is enhanced with the selection of the proper protein-stamp-substrate combination. In addition, detergent studies have shown that detergent-protein complexes detach from surfaces to a greater extent than proteins alone. Therefore, we hypothesized that stamp surface modification (termed here a release layer) can enhance polylysine transfer and benefit cell growth on microstamped substrates. We found unmodified stamps to transfer insufficient polylysine to support good cell survival of hippocampal neurons in a widely used serum-free, reduced-glia cell culture system. However, with modified stamps neuronal growth was reliably good. This enhanced cell growth can be attributed to the increased polylysine transfer due to the release layer rather than increased loading onto the stamp. This enhancement was found to be even greater for two-month old stamps that were stored in water. Furthermore, the physicochemical properties of the release layer can modulate the loading process. Thus, our data supports the conclusions that the release layer: (1) modulates polylysine loading, (2) enhances polylysine transfer, (3) enhances cellular growth on microstamped substrates, and (4) extends the durability (defined as the number of times a stamp can be reused) of PDMS microstamps.

Simulation and evaluation of elemental mercury concentration increase in flue gas across a wet scrubber.

Experimental data from a laboratory-scale wet scrubber simulator confirmed that oxidized mercury, Hg2+, can be reduced by aqueous S(IV) (sulfite and/or bisulfite) species and results in elemental mercury (HgO) emissions under typical wet FGD scrubber conditions. The S(IV)-induced Hg2+ reduction and Hg0 emission mechanism can be described by a model which assumes that only a fraction of the Hg2+ can be reduced, and the rate-controlling step of the overall process is a first-order reaction involving the Hg-S(IV) complexes. Experimental data and model simulations predict that the Hg2+ in the flue gas can cause rapid increase of Hg0 concentration in the flue gas across a FGD scrubber. Forced oxidation can enhance Hg2+ reduction and Hg0 emission by decreasing the S(IV) concentration in the scrubbing liquor. The model predictions also indicate that flue gas Hg0 increase across a wet FGD scrubber can be reduced by decreasing the pH, increasing S(IV) concentration, and lowering the temperature.

Characterization and reduction of formaldehyde emissions from a low-VOC latex paint.

The patterns of formaldehyde emission from a low volatile organic compound (VOC) latex paint applied to gypsum board were measured and analyzed by small environmental chamber tests. It was found that the formaldehyde emissions resulted in a sharp increase of chamber air formaldehyde concentration to a peak followed by transition to a long-term slow decay. A semi-empirical first-order decay in-series model was developed to interpret the chamber data. The model characterized the formaldehyde emissions from the paint in three stages: an initial "puff" of instant release, a fast decay, and a final stage of slow decay controlled by a solid-phase diffusion process that can last for more than a month. The model was also used to estimate the peak concentration and the amount of formaldehyde emitted during each stage. The formaldehyde sources were investigated by comparing emission patterns and modeling outcomes of different paint formulations. The biocide used to preserve the paint was found to be a major source of the formaldehyde. Chamber test results demonstrated that replacing the preservative with a different biocide for the particular paint tested resulted in an approximate reduction of 55% of formaldehyde emissions. But the reduction affected only the third-stage long-term emissions.

Evaluation of Sink Effects on VOCs from a Latex Paint.

The sink strength of two common indoor materials, a carpet and a gypsum board, was evaluated by environmental chamber tests with four volatile organic compounds (VOCs): propylene glycol, ethylene glycol, 2-(2-butoxyethoxy)ethanol (BEE), and Texanol. These oxygenated compounds represent the major VOCs emitted from a latex paint. Each chamber test included two phases. Phase 1 was the dosing/sorption period during which sink materials (pieces of carpet and gypsum board samples) were exposed to the four VOCs. The sink strength of each material tested was characterized by the amount of the VOCs adsorbed or absorbed. Phase 2 was the purging/de-sorption period during which the chambers with the dosed sink materials were flushed with purified air. The reemission rates of the adsorbed VOCs from the sinks were reflected by the amount of the VOCs being flushed. Phase 1 results indicated that the sink strength for the four target compounds is more than 1 order of magnitude higher than that for other VOCs previously tested by the U.S. Environmental Protection Agency (EPA). The high sink strength reflected the unusually high sorption capacity of common indoor materials for the four VOCs. Phase 2 results showed that reemission was an extremely slow process. If all the VOCs adsorbed were reemittable, it would take more than a year to completely flush out the VOCs from the sink materials tested. The long reemission process can result in chronic and low-level exposure to the VOCs after painting interior walls and surfaces.