A bistable, multiport valve enables microformulators creating microclinical analyzers that reveal aberrant glutamate metabolism in astrocytes derived from a tuberous sclerosis patient.

There is a need for valves and pumps that operate at the microscale with precision and accuracy, are versatile in their application, and are easily fabricated. To that end, we developed a new rotary planar multiport valve to faithfully select solutions (contamination = 5.22 ± 0.06 ppb) and a rotary planar peristaltic pump to precisely control fluid delivery (flow rate = 2.4 ± 1.7 to 890 ± 77 µL/min). Both the valve and pump were implemented in a planar format amenable to single-layer soft lithographic fabrication. These planar microfluidics were actuated by a rotary motor controlled remotely by custom software. Together, these two devices constitute an innovative microformulator that was used to prepare precise, high-fidelity mixtures of up to five solutions (deviation from prescribed mixture = ±|0.02 ± 0.02| %). This system weighed less than a kilogram, occupied around 500 cm3, and generated pressures of 255 ± 47 kPa. This microformulator was then combined with an electrochemical sensor creating a microclinical analyzer (µCA) for detecting glutamate in real time. Using the chamber of the µCA as an in-line bioreactor, we compared glutamate homeostasis in human astrocytes differentiated from human-induced pluripotent stem cells (hiPSCs) from a control subject (CC-3) and a Tuberous Sclerosis Complex (TSC) patient carrying a pathogenic TSC2 mutation. When challenged with glutamate, TSC astrocytes took up less glutamate than control cells. These data validate the analytical power of the µCA and the utility of the microformulator by leveraging it to assess disease-related alterations in cellular homeostasis.

Multianalyte Physiological Microanalytical Devices.

Advances in scientific instrumentation have allowed experimentalists to evaluate well-known systems in new ways and to gain insight into previously unexplored or poorly understood phenomena. Within the growing field of multianalyte physiometry (MAP), microphysiometers are being developed that are capable of electrochemically measuring changes in the concentration of various metabolites in real time. By simultaneously quantifying multiple analytes, these devices have begun to unravel the complex pathways that govern biological responses to ischemia and oxidative stress while contributing to basic scientific discoveries in bioenergetics and neurology. Patients and clinicians have also benefited from the highly translational nature of MAP, and the continued expansion of the repertoire of analytes that can be measured with multianalyte microphysiometers will undoubtedly play a role in the automation and personalization of medicine. This is perhaps most evident with the recent advent of fully integrated noninvasive sensor arrays that can continuously monitor changes in analytes linked to specific disease states and deliver a therapeutic agent as required without the need for patient action.

Improved efficiency in clinical workflow of reporting measured oncology lesions via PACS-integrated lesion tracking tool.

OBJECTIVE. Imaging provides evidence for the response to oncology treatment by the serial measurement of reference lesions. Unfortunately, the identification, comparison, measurement, and documentation of several reference lesions can be an inefficient process. We tested the hypothesis that optimized workflow orchestration and tight integration of a lesion tracking tool into the PACS and speech recognition system can result in improvements in oncologic lesion measurement efficiency. SUBJECTS AND METHODS. A lesion management tool tightly integrated into the PACS workflow was developed. We evaluated the effect of the use of the tool on measurement reporting time by means of a prospective time-motion study on 86 body CT examinations with 241 measureable oncologic lesions with four radiologists. RESULTS. Aggregated measurement reporting time per lesion was 11.64 seconds in standard workflow, 16.67 seconds if readers had to register measurements de novo, and 6.36 seconds for each subsequent follow-up study. Differences were statistically significant (p < 0.05) for each reader, except for one difference for one reader. CONCLUSION. Measurement reporting time can be reduced by using a PACS workflow-integrated lesion management tool, especially for patients with multiple follow-up examinations, reversing the onetime efficiency penalty at baseline registration.

Preferences for structured reporting of measurement data: an institutional survey of medical oncologists, oncology registrars, and radiologists.

RATIONALE AND OBJECTIVES: The aim of this study was to determine whether key radiology report "consumers" in our institution prefer structured measurement reporting in a dedicated report section over the current practice of embedding measurements throughout the "Findings" section, given the availability of new tools for quantitative imaging interpretation that enable automated structured reporting of measurement data. MATERIALS AND METHODS: Oncologic clinicians and radiologists at our institution were surveyed regarding their preferences for a standard report versus three reports each having uniquely formatted dedicated "Measurements" sections and regarding their impressions of various characteristics of report quality demonstrated by these reports. The online survey was completed by 25 radiologists, 16 oncologists, and 17 oncology nurses and research assistants (registrars). RESULTS: Aggregation of respondents' preferences by group into single orderings using the Kemeny-Young method revealed that both oncology groups preferred all proposed reports to the standard report but that radiologists only preferred two of the proposed reports to the standard report. All preferences for proposed reports in the two oncology groups were statistically significant based on Wilcoxon tests, but the preference for only one of the proposed reports was significant for radiologists. Additional results suggest that these preferences are driven by respondent favor for the readability of and confidence conveyed by the proposed reports compared to the standard report. CONCLUSIONS: Oncologic clinicians responding to our survey preferred communication of lesion measurements in a separate report section to the current practice of embedding measurements throughout the "Findings" section, based on their assessments of reports containing simulated measurement sections assembled from a single sample report using standardized formatting.

Vascular pulsatility in patients with a pulsatile- or continuous-flow ventricular assist device.

OBJECTIVE: We sought to investigate differences in indices of pulsatility between patients with normal ventricular function and patients with heart failure studied at the time of implantation with continuous-flow or pulsatile-flow left ventricular assist devices. METHODS: Eight patients with normal ventricular function and 22 patients with heart failure were studied. A high-fidelity aortic and left ventricular pressure catheter was inserted retrograde through the aortic valve into the left ventricle, and transit-time flow probes were placed on the aorta and device outflow graft. Hemodynamic waveforms were recorded at native heart rate before cardiopulmonary bypass and over a range of device flow rates controlled by adjusting beat rate or rpm. These data were used to calculate vascular input impedance and 2 indices of vascular pulsatility: energy-equivalent pressure and surplus hemodynamic energy. RESULTS: At low support levels, pulsatile support restored surplus hemodynamic energy to within 2.5% of normal values, whereas continuous support diminished surplus energy by more than 93%. At high support levels, pulsatile support augmented surplus energy by 49% over normal values, whereas continuous support further diminished surplus energy by 97%. Pulsatile support diminished vascular impedance from baseline failure values, whereas continuous support increased impedance. Vascular impedances at baseline for patients undergoing pulsatile and continuous support and during pulsatile support revealed normal vascular compliance, whereas impedance during continuous support indicated a loss of compliance (or "stiffening") of the vasculature. CONCLUSION: These results suggest that selection of device type and flow rate can influence vascular pulsatility and input impedance, which might affect clinical outcomes.

Selective excitation of myelin water using inversion-recovery-based preparations.

T1 and T2 relaxation of excised frog sciatic nerve water was characterized at 7 T. Based on these findings, optimal timings for multiple inversion-recovery magnetization preparations were determined to selectively excite the so-called myelin-water T2 component. Subsequent double inversion-recovery and triple inversion-recovery preparations were used in combination with CPMG acquisitions to experimentally determine optimal timings and effect of the preparation. Using double inversion-recovery, optimal timings were found to excite magnetization that is predominantly (approximately 93%) derived from the myelin-water component. Greater selectivity (approximately 96%) was found by extending the preparation to triple inversion-recovery, at the price of decreasing SNR by a factor of approximately 2.

PASTA: pointwise assessment of streamline tractography attributes.

Diffusion tensor MRI tractography aims to reconstruct noninvasively the 3D trajectories of white matter fasciculi within the brain, providing neuroscientists and clinicians with a potentially useful tool for mapping brain architecture. While this technique is widely used to visualize white matter pathways, the associated uncertainty in fiber orientation and artifacts have, to date, not been visualized in conjunction with the trajectory data. In this work, the bootstrap method was used to determine the distributions of diffusion indices such as trace and anisotropy, together with the uncertainty in fiber orientation. A novel visualization scheme was developed to encode this information at each point along reconstructed trajectories. By integrating these schemes into a graphical user interface, a new tool which we call PASTA (Pointwise Assessment of Streamline Tractography Attributes) was created to facilitate identification of artifacts in tractography that would otherwise go undetected.