Increasing the packing density of assays in paper-based microfluidic devices.

Paper-based devices have a wide range of applications in point-of-care diagnostics, environmental analysis, and food monitoring. Paper-based devices can be deployed to resource-limited countries and remote settings in developed countries. Paper-based point-of-care devices can provide access to diagnostic assays without significant user training to perform the tests accurately and timely. The market penetration of paper-based assays requires decreased device fabrication costs, including larger packing density of assays (i.e., closely packed features) and minimization of assay reagents. In this review, we discuss fabrication methods that allow for increasing packing density and generating closely packed features in paper-based devices. To ensure that the paper-based device is low-cost, advanced fabrication methods have been developed for the mass production of closely packed assays. These emerging methods will enable minimizing the volume of required samples (e.g., liquid biopsies) and reagents in paper-based microfluidic devices.

A Macro-Structural Dispersion Characteristic of Brain White Matter and Its Application to Bipolar Disorder.

OBJECTIVE: Our goal is to find distinct characteristics of brain white matter in bipolar disorder, of which the development of diagnostic imaging measures is necessary for early diagnosis and prospective studies. METHODS: Given a tractogram dataset which is a dense set of white matter fiber pathways of the whole brain obtained from diffusion magnetic resonance imaging, we propose to compute a global measure for a voxel from the dispersion statistics of a set of fibers which indicates the complexity of the white matter voxel not locally but at macroscopic scales. RESULTS: Our findings demonstrate that macro-structural dispersion information is significant for discrimination of the bipolar patients from the healthy controls, particularly in the frontally associative bundles such as cingulum and inferior occipito-frontal fascicles. CONCLUSION: The proposed measure is as informative as the local diffusion measures for the detection of changes in the white matter regions. SIGNIFICANCE: Our findings show that the proposed measure is a potential diagnostic imaging marker in bipolar disorder and the proposed novel dispersion map of the brain could be used for other neurological applications.

Real-Time Performance of a Tactile Neuroprosthesis on Awake Behaving Rats.

With the advancement of electrode and equipment technology, neuroprosthetics have become a promising alternative to partially compensate for the loss of sensorimotor function in amputees and patients with neurological diseases. Cortical neural interfaces are suitable especially for spinal cord injuries and amyotrophic lateral sclerosis. Although considerable success has been achieved in the literature by spike decoding of motor signals from the human brain, somatosensory feedback is essential for better motor control, interaction with objects, and the embodiment of prosthetic devices. In this paper, we present a tactile neuroprosthesis for rats based on intracortical microstimulation (ICMS). The rats wore mechanically-isolated boots covered with tactile sensors while performing a psychophysical detection task. The vibrotactile stimuli were measured by the artificial sensors and by using a real-time processor, this information was converted to electrical current pulses for ICMS. Some parameters of the real-time processor algorithm were specific to individual rats and were based on psychometric equivalence functions established earlier. Rats could detect the effects of the vibrotactile stimuli better (i.e., higher sensitivity indices) when the tactile neuroprosthesis was switched on compared to the boot only condition during active movement. In other words, the rats could decode the tactile information embedded in ICMS and use that in a behaviorally relevant manner. The presented animal model without peripheral nerve injury or amputation is also a promising tool to test various hardware and software components of neuroprosthetic systems in general.

Utilization of MR angiography in perfusion imaging for identifying arterial input function.

OBJECTIVE: This research utilizes magnetic resonance angiography (MRA) to identify arterial locations during the parametric evaluation of concentration time curves (CTCs), and to prevent shape distortions in arterial input function (AIF). MATERIALS AND METHODS: We carried out cluster analysis with the CTC parameters of voxels located within and around the middle cerebral artery (MCA). Through MRA, we located voxels that meet the AIF criteria and those with distorted CTCs. To minimize partial volume effect, we re-scaled the time integral of CTCs by the time integral of venous output function (VOF). We calculated the steady-state value to area under curve ratio (SS:AUC) of VOF and used it as a reference in selecting AIF. CTCs close to this reference value (selected AIF) and those far from it were used (eliminated AIF) to compute cerebral blood flow (CBF). RESULTS: Eliminated AIFs were found to be either on or anterior to MCA, whereas selected AIFs were located superior, inferior, posterior, or anterior to MCA. If the SS:AUC of AIF was far from the reference value, CBF was either under- or over-estimated by a maximum of 41.1 ± 14.3 and 36.6 ± 19.2%, respectively. CONCLUSION: MRA enables excluding voxels on the MCA during cluster analysis, and avoiding the risk of shape distortions.

Determination of neural fiber connections based on data structure algorithm.

The brain activity during perception or cognition is mostly examined by functional magnetic resonance imaging (fMRI). However, the cause of the detected activity relies on the anatomy. Diffusion tensor magnetic resonance imaging (DTMRI) as a noninvasive modality providing in vivo anatomical information allows determining neural fiber connections which leads to brain mapping. Still a complete map of fiber paths representing the human brain is missing in literature. One of the main drawbacks of reliable fiber mapping is the correct detection of the orientation of multiple fibers within a single imaging voxel. In this study a method based on linear data structures is proposed to define the fiber paths regarding their diffusivity. Another advantage of the proposed method is that the analysis is applied on entire brain diffusion tensor data. The implementation results are promising, so that the method will be developed as a rapid fiber tractography algorithm for the clinical use as future study.

The development of a new orthosis (neuro-orthosis) for patients with carpal tunnel syndrome: its effect on the function and strength of the hand.

Static wrist orthoses (SWOs) are used in the treatment of carpal tunnel syndrome (CTS) with some drawbacks. As an alternate approach to SWOs, an active closed-loop wrist control strategy based on the principles of functional electrical stimulation was proposed to limit wrist movements. The purpose of the study was to determine whether the proposed 'neuro-orthosis' (NeO) system resulted in less restriction in the hand compared to clinically accepted custom-made SWOs while limiting the wrist movements. A case-control study was designed to determine the specific effects of the system on patients with CTS. A total of 24 right-handed female volunteers (12: CTS, 12: healthy) participated in the study. Function, dexterity, and strengths were measured under three different testing conditions: without orthosis, with SWO, and with the NeO system. Maximum angles in one subtest while the NeO system was on and off and general discomfort levels in SWO and NeO test conditions were recorded. The NeO system resulted in less restriction with respect to SWO and provided considerable angular limitation compared to placebo. It was concluded that the proposed prototype control system can be a good candidate to limit the wrist movements in place of SWOs with a better degree of freedom in patients with CTS.

Fiber tracking: a recursive stack algorithmic approach.

In diffusion tensor magnetic resonance imaging (DT-MRI), each voxel is assigned a tensor that describes local water diffusion. In this study, the eigenvectors and eigenvalues of the diffusion tensor D are analyzed based on stack linked list algorithm. The aim of the study is to develop a reliable and rapid tractography algorithm. In our sample, 60 diffusion weighted human brain images and a null image namely the T2 image creating a set of intensity images of size 256x256x60x30 have been examined. The eigensystem of D is calculated in every pixel, apparent diffusion coefficient ADC is represented with respect to D. The idea of the proposed method is to accomplish the fiber pathway by starting from a single, selected node taking every node in other words all the information of the eigensystem of the whole brain into account. Developing a reliable and rapid fiber tracking algorithm for the clinical use regarding to the verified results is the future study of the work in progress.

Elimination of RF inhomogeneity effects in segmentation.

There are various methods proposed for the segmentation and analysis of MR images. However the efficiency of these techniques is effected by various artifacts that occur in the imaging system. One of the most encountered problems is the intensity variation across an image. To overcome this problem different methods are used. In this paper we propose a method for the elimination of intensity artifacts in segmentation of MRI images. Inter imager variations are also minimized to produce the same tissue segmentation for the same patient. A well-known multivariate classification algorithm, maximum likelihood is employed to illustrate the enhancement in segmentation.

GSM base station electromagnetic radiation and oxidative stress in rats.

The ever increasing use of cellular phones and the increasing number of associated base stations are becoming a widespread source of nonionizing electromagnetic radiation. Some biological effects are likely to occur even at low-level EM fields. In this study, a gigahertz transverse electromagnetic (GTEM) cell was used as an exposure environment for plane wave conditions of far-field free space EM field propagation at the GSM base transceiver station (BTS) frequency of 945 MHz, and effects on oxidative stress in rats were investigated. When EM fields at a power density of 3.67 W/m2 (specific absorption rate = 11.3 mW/kg), which is well below current exposure limits, were applied, MDA (malondialdehyde) level was found to increase and GSH (reduced glutathione) concentration was found to decrease significantly (p < 0.0001). Additionally, there was a less significant (p = 0.0190) increase in SOD (superoxide dismutase) activity under EM exposure.

Simulated dataset for verification & validation of DT-MRI analyzing tools.

In diffusion tensor MRI (DT-MRI), each voxel is assigned a tensor that describes local water diffusion. In this study, a simulated DT dataset for analyzing the diffusion characteristics is developed to verify and validate DT images postprocessed with various DT analyzing codes. This module is intended as a resource for DT-MRI analyzing tools to verify and validate the analysis results. The b factor in our study is the B matrix of size 1x7. In our sample, 6 diffusion weighted images and a null image namely the T2 image creating a set of intensity images of size 256x256x7 is generated for the analysis. The idea is to fullfil the routine DT analysis from the apparent diffusion coefficient ADC image instead of the DT images. This inverse analysis methodology is preparing the basis of the image information to be investigated as known values. According to the Stejskal Tanner equation, D= [Dxx, Dyy, Dzz, Dxy, Dxz, Dyz] is calculated in the algorithm. After the validation of the algorithm with the simulated diffusion tensor dataset, real MR data of human brain and myocardium are used. The eigensystem D is calculated in every pixel, ADC is represented with respect to D. The other characteristic values of diffusivity namely fractional (FA) and relative (RA) anisotropy values are calculated. Developing a reliable and rapid tractography algorithm for the clinical use regarding to these verified results is the future study of the work in progress.

Quantitative proton MR spectroscopic findings of cortical reorganization in the auditory cortex of musicians.

BACKGROUND AND PURPOSE: Brain has a capacity for reorganization that enables use-dependent adaptations to acquire skills. Previous studies demonstrated morphometric and functional use-dependent changes in the brains of musicians. The purpose of this study was to investigate the differences in metabolite concentrations in the planum temporale, an area strongly associated with the processing of music perception, between trained musicians and non-musicians. We hypothesized that the microscopic changes leading to use-dependent adaptations in brain might cause neurometabolite changes that could be detected with quantitative proton MR spectroscopy. METHODS: We performed quantitative proton MR spectroscopy in the left planum temporale of 10 musicians (six men and four women; age range, 20-37 years) and in those of 10 age- and sex-matched control subjects who had no musical training. We calculated the major metabolite concentrations in the left planum temporale. RESULTS: The difference in N-acetylaspartate (NAA) concentrations between the musicians and the non-musician control subjects was statistically significant (P <.01). No significant difference was noted in the choline and creatine concentrations between the musicians and the non-musician control subjects (P >.05). The NAA concentration of the musicians correlated with the total duration of musical training and activity (r=0.733, P <.05). CONCLUSION: Long-term, professional musical activity caused significant changes in the neurometabolite concentrations that might reflect the physiologic mechanism(s) of use-dependent adaptation in the brains of musicians.

Evaluation of hemodynamic perfusion MR images.

Perfusion normally refers to the delivery of blood at the level of capillaries. Hemodynamic perfusion magnetic resonance (MR) imaging has been used in clinics for a series of applications including tumor characterization (histological type diagnosis and grading), diagnosis and the follow up of stroke, and several other disorders. For this study a platform to investigate the theoretical basis of perfusion imaging was developed. Using dynamic measurements of contrast agents in magnetic resonance imaging (MRI) relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and mean transit time (MTT) are calculated. These three parameters are quantized, and displayed as color images for diagnostic and follow up studies. The comparative studies in MR perfusion must address issues such as; image registration, region of interest (ROI) selection, threshold identification and quantization of rCBV, rCBF and rMTT. The evaluation process involved the comparison of the diagnostic capabilities of the three perfusion images (rCBV, rCBF, MTT). Digital Substraction angiography was used as the gold standard in these comparisons. The study group comprises 16 patients with the diagnosis of subarachnoid bleeding and intracranial aneurysms. The proposed cerebral MR perfusion analysis system has been accepted by the radiologists as a useful tool for their perfusion studies and clinical evaluation.