BOLD signal compartmentalization based on the apparent diffusion coefficient.

Functional MRI (fMRI) can detect blood oxygenation level dependent (BOLD) hemodynamic responses secondary to neuronal activity. The most commonly used method for detecting fMRI signals is the gradient-echo echo-planar imaging (EPI) technique because of its sensitivity and speed. However, it is generally believed that a significant portion of these signals arises from large veins, with additional contribution from the capillaries and parenchyma. Early experiments using diffusion-weighted gradient-echo EPI have suggested that intra-voxel incoherent motion (IVIM) weighting inherent in the sequence can selectively attenuate contributions from different vessels based on the differences in the mobility of the blood within them. In the present study, we used similar approach to characterize the apparent diffusion coefficient (ADC) distribution within the activated areas of BOLD contrast. It is shown that the voxel values of the ADCs obtained from this technique can infer various vascular contributions to the BOLD signal.

Improved delineation of short cortical association fibers and gray/white matter boundary using whole-brain three-dimensional diffusion tensor imaging at submillimeter spatial resolution.

Recent emergence of human connectome imaging has led to a high demand on angular and spatial resolutions for diffusion magnetic resonance imaging (MRI). While there have been significant growths in high angular resolution diffusion imaging, the improvement in spatial resolution is still limited due to a number of technical challenges, such as the low signal-to-noise ratio and high motion artifacts. As a result, the benefit of a high spatial resolution in the whole-brain connectome imaging has not been fully evaluated in vivo. In this brief report, the impact of spatial resolution was assessed in a newly acquired whole-brain three-dimensional diffusion tensor imaging data set with an isotropic spatial resolution of 0.85 mm. It was found that the delineation of short cortical association fibers is drastically improved as well as the definition of fiber pathway endings into the gray/white matter boundary-both of which will help construct a more accurate structural map of the human brain connectome.

Local kinetic interpretation of entropy production through reversed diffusion.

The time reversal of stochastic diffusion processes is revisited with emphasis on the physical meaning of the time-reversed drift and the noise prescription in the case of multiplicative noise. The local kinematics and mechanics of free diffusion are linked to the hydrodynamic description. These properties also provide an interpretation of the Pope-Ching formula for the steady-state probability density function along with a geometric interpretation of the fluctuation-dissipation relation. Finally, the statistics of the local entropy production rate of diffusion are discussed in the light of local diffusion properties, and a stochastic differential equation for entropy production is obtained using the Girsanov theorem for reversed diffusion. The results are illustrated for the Ornstein-Uhlenbeck process.

A Diffusion MRI Tractography Connectome of the Mouse Brain and Comparison with Neuronal Tracer Data.

Interest in structural brain connectivity has grown with the understanding that abnormal neural connections may play a role in neurologic and psychiatric diseases. Small animal connectivity mapping techniques are particularly important for identifying aberrant connectivity in disease models. Diffusion magnetic resonance imaging tractography can provide nondestructive, 3D, brain-wide connectivity maps, but has historically been limited by low spatial resolution, low signal-to-noise ratio, and the difficulty in estimating multiple fiber orientations within a single image voxel. Small animal diffusion tractography can be substantially improved through the combination of ex vivo MRI with exogenous contrast agents, advanced diffusion acquisition and reconstruction techniques, and probabilistic fiber tracking. Here, we present a comprehensive, probabilistic tractography connectome of the mouse brain at microscopic resolution, and a comparison of these data with a neuronal tracer-based connectivity data from the Allen Brain Atlas. This work serves as a reference database for future tractography studies in the mouse brain, and demonstrates the fundamental differences between tractography and neuronal tracer data.

Correction for Eddy Current-Induced Echo-Shifting Effect in Partial-Fourier Diffusion Tensor Imaging.

In most diffusion tensor imaging (DTI) studies, images are acquired with either a partial-Fourier or a parallel partial-Fourier echo-planar imaging (EPI) sequence, in order to shorten the echo time and increase the signal-to-noise ratio (SNR). However, eddy currents induced by the diffusion-sensitizing gradients can often lead to a shift of the echo in k-space, resulting in three distinct types of artifacts in partial-Fourier DTI. Here, we present an improved DTI acquisition and reconstruction scheme, capable of generating high-quality and high-SNR DTI data without eddy current-induced artifacts. This new scheme consists of three components, respectively, addressing the three distinct types of artifacts. First, a k-space energy-anchored DTI sequence is designed to recover eddy current-induced signal loss (i.e., Type 1 artifact). Second, a multischeme partial-Fourier reconstruction is used to eliminate artificial signal elevation (i.e., Type 2 artifact) associated with the conventional partial-Fourier reconstruction. Third, a signal intensity correction is applied to remove artificial signal modulations due to eddy current-induced erroneous T2(∗) -weighting (i.e., Type 3 artifact). These systematic improvements will greatly increase the consistency and accuracy of DTI measurements, expanding the utility of DTI in translational applications where quantitative robustness is much needed.

Modelling meso-scale diffusion processes in stochastic fluid bio-membranes

The space–time dynamics of rigid inhomogeneities (inclusions) free to move in a randomly fluctuating fluid bio-membrane is derived and numerically simulated as a function of the membrane shape changes. Both vertically placed (embedded) inclusions and horizontally placed (surface) inclusions are considered. The energetics of the membrane, as a two-dimensional (2D) meso-scale continuum sheet, is described by the Canham–Helfrich Hamiltonian, with the membrane height function treated as a stochastic process. The diffusion parameter of this process acts as the link coupling the membrane shape fluctuations to the kinematics of the inclusions. The latter is described via Ito stochastic differential equation. In addition to stochastic forces, the inclusions also experience membrane-induced deterministic forces. Our aim is to simulate the diffusion-driven aggregation of inclusions and show how the external inclusions arrive at the sites of the embedded inclusions. The model has potential use in such emerging fields as designing a targeted drug delivery system.

The effect of reflow process on the contact resistance and reliability of anisotropic conductive film interconnection for flip chip on flex applications

The work presented in this paper focuses on the effect of reflow process on the contact resistance and reliability of anisotropic conductive film (ACF) interconnection. The contact resistance of ACF interconnection increases after reflow process due to the decrease in contact area of the conducting particles between the mating I/O pads. However, the relationship between the contact resistance and bonding parameters of the ACF interconnection with reflow treatment follows the similar trend to that of the as-bonded (i.e. without reflow) ACF interconnection. The contact resistance increases as the peak temperature of reflow profile increases. Nearly 40% of the joints were found to be open after reflow with 260 °C peak temperature. During the reflow process, the entrapped (between the chip and substrate) adhesive matrix tries to expand much more than the tiny conductive particles because of the higher coefficient of thermal expansion, the induced thermal stress will try to lift the bump from the pad and decrease the contact area of the conductive path and eventually, leading to a complete loss of electrical contact. In addition, the environmental effect on contact resistance such as high temperature/humidity aging test was also investigated. Compared with the ACF interconnections with Ni/Au bump, higher thermal stress in the Z-direction is accumulated in the ACF interconnections with Au bump during the reflow process owing to the higher bump height, thus greater loss of contact area between the particles and I/O pads leads to an increase of contact resistance and poorer reliability after reflow.

Experimental and modeling analysis of the reliability of the anisotropic conductive films

Experiments as well as computer modeling methods have been used to investigate the effect of the solder reflow process on the electrical characteristics and reliability of anisotropic conductive film (ACF) interconnections. In the experiments, the contact resistance of the ACF interconnections was found to increase after a subsequent reflow and the magnitude of this increase was strongly correlated to the peak temperature of the reflow profile. In fact, nearly 40 percent of the joints were opened (i.e. lifted away from the pad) after the reflow with a peak temperature of 260 OC while no openings was observed when the peak temperature was 210 "C. It is believed that the CTE mismatch between the polymer particle and the adhesive matrix is the main cause of this contact degradation. To understand this phenomenon better, a 3-D model of an ACF joint structure was built and Finite Element Analysis was used to predict the stress distrihution in the conductive particles, adhesive matrix and metal pads during the reflow process. The effects of the peak temperature, the CTE of the adhesive matrix and the bump height on the reliability of the ACF interconnections were discussed.

Effects of reflow process on the reliability of flip chip on flex interconnections using anisotropic conductive adhesives

In this paper, the effects of the solder reflow process on the reliability of anisotropic conductive film (ACF) interconnections for flip chip on flex (FCOF) applications are investigated. Experiments as well as computer modeling methods have been used. In the experiments, it was found that the contact resistance of ACF joints increased after the subsequent reflow process, and the magnitude of this increase was strongly correlated to the peak temperature of the reflow profile. Nearly 40% of the joints were opened (i.e. lifted away from the pad) after the reflow process with 260 °C peak temperature while no opening was observed when the peak temperature was 210 °C. It is believed that the CTE mismatch between the polymer particle and the adhesive matrix is the main cause of this contact degradation. It was also found that the ACF joints after the reflow process with 210 °C peak temperature showed a high ability to resist water absorption under steady state 85 °C/85%RH conditions, probably because the curing degree of the ACF was improved during the reflow process. To give a good understanding, a 3D model of an ACF joint structure was built and finite element analysis was used to predict the stress distribution in the conductive particles, adhesive matrix and metal pads during the reflow process.

Study of Anisotropic Conductive Adhesive Joint Behaviour under 3-Point Bending

Flip chip interconnections using anisotropic conductive film (ACF) are now a very attractive technique for electronic packaging assembly. Although ACF is environmentally friendly, many factors may influence the reliability of the final ACF joint. External mechanical loading is one of these factors. Finite element analysis (FEA) was carried out to understand the effect of mechanical loading on the ACF joint. A 3-dimensional model of adhesively bonded flip chip assembly was built and simulations were performed for the 3-point bending test. The results show that the stress at its highest value at the corners, where the chip and ACF were connected together. The ACF thickness was increased at these corner regions. It was found that higher mechanical loading results in higher stress that causes a greater gap between the chip and the substrate at the corner position. Experimental work was also carried out to study the electrical reliability of the ACF joint with the applied bending load. As per the prediction from FEA, it was found that at first the corner joint failed. Successive open joints from the corner towards the middle were also noticed with the increase of the applied load.

Moisture Effects on the Reliability of Anisotropic Conductive Films

Anisotropic conductive film (ACF) which consists of an adhesive epoxy matrix and randomly distributed conductive particles are widely used as the connection material for electronic devices with high I/O counts. However, for the semiconductor industry the reliability of the ACF is still a major concern due to a lack of experimental reliability data. This paper reports an investigation into the moisture effects on the reliability of ACF interconnections in the flip-chip-on-flex (FCOF) applications. A macro-micro 3D finite element modeling technique was used in order to make the multi-length-scale modeling of the ACF flip chip possible. The purposes of this modeling work was to understand the role that moisture plays in the failure of ACF flip chips, and to look into the influence of physical properties and geometric characteristics, such as the coefficient of the moisture expansion (CME), Young's modulus of the adhesive matrix and the bump height on the reliability of the ACF interconnections in a humid environment. Simulation results suggest that moisture-induced swelling of the adhesive matrix is the major cause of the ACF joint opening. Modeling results are consistent with the findings in the experimental work.

Effects of solder reflow on the reliability of flip-chip on flex interconnections using anisotropic conductive adhesives

This work describes the work of an investigation of the effects of solder reflow process on the reliability of anisotropic conductive film (ACF) interconnection for flip-chip on flex (FCOF) applications. Experiments as well as computer modeling methods have been used. The results show that the contact resistance of ACF interconnections increases after the reflow and the magnitude of the increase is strongly correlated to the peak reflow temperature. In fact, nearly 40 percent of the joints are open when the peak reflow temperature is 260°C, while there is no opening when the peak temperature is 210°C. It is believed that the coefficient of thermal expansion (CTE) mismatch between the polymer particle and the adhesive matrix is the main cause of this contact degradation. To understand this phenomenon better, a three-dimensional (3-D) finite element (FE) model of an ACF joint has been analyzed in order to predict the stress distribution in the conductive particles, adhesive matrix and metal pads during the reflow process. The stress level at the interface between the particle and its surrounding materials is significant and it is the highest at the interface between the particle and the adhesive matrix.

Macro-micro modelling of moisture induced stresses in an ACF flip chip assembly

Purpose – This paper discusses the use of modelling techniques to predict the reliability of an anisotropic conductive film (ACF) flip chip in a humid environment. The purpose of this modelling work is to understand the role that moisture plays in the failure of ACF flip chips. Design/methodology/approach – A 3D macro-micro finite element modelling technique was used to determine the moisture diffusion and moisture-induced stresses inside the ACF flip chip. Findings – The results show that the ACF layer in the flip chip can be expected to be fully saturated with moisture after 3?h at 121°C, 100%RH, 2?atm test conditions. The swelling effect of the adhesive due to this moisture absorption causes predominately tensile stress at the interface between the adhesive and the metallization, which could cause a decrease in the contact area, and therefore an increase in the contact resistance. Originality/value – This paper introduces a macro-micro modelling technique which enables more detailed 3D modelling analysis of an ACF flip chip than previously.