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Global identifiability of linear compartmental models--a computer algebra algorithm.

A priori global identifiability deals with the uniqueness of the solution for the unknown parameters of a model and is, thus, a prerequisite for parameter estimation of biological dynamic models. Global identifiability is however difficult to test, since it requires solving a system of algebraic nonlinear equations which increases both in nonlinearity degree and number of terms and unknowns with increasing model order. In this paper, a computer algebra tool, GLOBI (GLOBal Identifiability) is presented, which combines the topological transfer function method with the Buchberger algorithm, to test global identifiability of linear compartmental models. GLOBI allows for the automatic testing of a priori global identifiability of general structure compartmental models from general multi input-multi output experiments. Examples of usage of GLOBI to analyze a priori global identifiability of some complex biological compartmental models are provided.

Algorithms↗

Regional cerebral cortical thinning in bipolar disorder.

OBJECTIVE: This study was conducted to explore differences in cortical thickness between subjects with bipolar disorder and healthy comparison subjects using cortical surface-based analysis. METHODS: Brain magnetic resonance images were acquired from 25 subjects with bipolar disorder and 21 healthy comparison subjects. Cortical surface-based analysis was conducted using the Freesurfer application. Group differences in cortical thickness, defined by the distance from gray/white boundary to the pial surface, were assessed using statistical difference maps. RESULTS: Subjects with bipolar disorder exhibited significantly decreased cortical thickness in left cingulate cortex, left middle frontal cortex, left middle occipital cortex, right medial frontal cortex, right angular cortex, right fusiform cortex and bilateral postcentral cortices, relative to healthy comparison subjects (all p < 0.001). Duration of illness in bipolar subjects was inversely correlated with the cortical thickness of the left middle frontal cortex. CONCLUSIONS: Cortical thinning was present in multiple prefrontal cortices in bipolar disorder. There was also cortical thinning in sensory and sensory association cortices, which has not been reported in previous studies using region-of-interest or voxel-based morphometry methods. Cortical thinning observed in the current study may be related to impairment of emotional, cognitive, and sensory processing in bipolar disorder but longitudinal studies will be necessary to test this hypothesis.

Adult↗

Bioheat transfer in a branching countercurrent network during hyperthermia.

A bioheat transfer model which computes the spatial variations in the arteriole, venule, and muscle temperatures in a human extremity under both resting and hyperthermic conditions is presented. This model uses the two-parameter model first proposed by Baish et al. to account for the heat exchange between tissue and the paired arterioles and venules that comprise the microcirculation. Thermoregulation of the muscle blood flow during hyperthermia is also incorporated into the model. Results show that even when the paired arteriole and venule are assumed to have equal radii, the mean temperature under both steady and transient conditions is not equal to the mean of the arteriole and venule blood temperatures. Tissue temperature profiles during hyperthermia computed with the three-equation model presented in this study are similar in shape and magnitude to those predicted by the traditional one-equation Pennes bioheat transfer model. This is due primarily to the influence of thermoregulatory mechanism in the heated muscle. The unexpected agreement is significant given the inherent relative simplicity of the traditional Pennes model. An "experimental" thermal conductivity is presented to relate the theoretical results to experimental procedures that are widely used to estimate the enhancement of conductivity by perfusion.

Arterioles↗

Experimental demonstration of noninvasive transskull adaptive focusing based on prior computed tomography scans.

Developing minimally invasive brain surgery by high-intensity focused ultrasound beams is of great interest in cancer therapy. However, the skull induces strong aberrations both in phase and amplitude, resulting in a severe degradation of the beam shape. Thus, an efficient brain tumor therapy would require an adaptive focusing, taking into account the effects of the skull. In this paper, we will show that the acoustic properties of the skull can be deduced from high resolution CT scans and used to achieve a noninvasive adaptive focusing. Simulations have been performed with a full 3-D finite differences code, taking into account all the heterogeneities inside the skull. The set of signals to be emitted in order to focus through the skull can thus be computed. The complete adaptive focusing procedure based on prior CT scans has been experimentally validated. This could have promising applications in brain tumor hyperthermia but also in transcranial ultrasonic imaging.

Acoustics↗

Prediction of backscatter coefficient in trabecular bones using a numerical model of three-dimensional microstructure.

A model of ultrasonic backscattering for cancellous bone saturated by water is proposed. This model assumes that scattering is caused by the solid trabeculae and describes the cancellous bone as a weak scattering medium. The backscatter coefficient is related to the spatial Fourier transform of bone microarchitecture and to the density and compressibility fluctuations between the solid trabeculae and the saturating fluid. The computations of the model make use of three-dimensional numerical images of bone microarchitecture, obtained by tomographic reconstructions with a 10 microm spatial resolution. With this model, the predictions of the frequency dependence and of the magnitude of the backscatter coefficient are reasonably accurate. The theoretical predictions are compared to experimental data obtained on 19 specimens. An accuracy error of approximately 1 dB was found (difference between the averaged experimental values and theoretical predictions). One limit of the model may come from inaccurate values of trabecular bone characteristics needed for the computations (density and longitudinal velocity), which are yet to be precisely determined for human trabecular bone. However, the model is only slightly sensitive to variations of bone material properties. It was found that an accuracy error of 2.2 dB at maximum resulted from inaccurate a priori values of bone material properties. A computation of the elastic mean free path in the medium suggests that multiple scattering plays a minor role in the working frequency bandwidth (0.4-1.2 MHz). It follows from these results that a weak scattering medium model may be appropriate to describe scattering from trabecular bone.

Aged↗

Modeling vocal fold motion with a hydrodynamic semicontinuum model.

Vocal fold (VF) motion is a fundamental process in voice production, and is also a challenging problem for numerical computation because the VF dynamics depend on nonlinear coupling of air flow with the response of elastic channels (VF), which undergo opening and closing, and induce internal flow separation. The traditional modeling approach makes use of quasisteady flow approximation or Bernoulli's law which ignores air compressibility, and is known to be invalid during VF opening. A hydrodynamic semicontinuum system for VF motion is presented. The airflow is modeled by a modified quasi-one-dimensional Euler system with coupling to VF velocity. The VF is modeled by a lumped two mass system with a built-in geometric condition on flow separation. The modified Euler system contains the Bernoulli's law as a special case, and is derivable from the two-dimensional compressible Navier-Stokes equations in the inviscid limit. The computational domain contains also solid walls next to VFs (flexible walls). It is shown numerically that several salient features of VFs are captured, especially transients such as the double peaks of the driving subglottal pressures at the opening and the closing stages of VF motion consistent with fully resolved two-dimensional direct simulations, and experimental data. The system is much simpler to compute than a VF model based on two-dimensional Navier-Stokes system.

Computer Simulation↗

An efficient grid sectoring method for calculations of the near-field pressure generated by a circular piston.

An analytical expression is derived for time-harmonic calculations of the near-field pressure produced by a circular piston. The near-field pressure is described by an efficient integral that eliminates redundant calculations and subtracts the singularity, which in turn reduces the computation time and the peak numerical error. The resulting single integral expression is then combined with an approach that divides the computational grid into sectors that are separated by straight lines. The integral is computed with Gauss quadrature in each sector, and the number of Gauss abscissas in each sector is determined by a linear mapping function that prevents large errors from occurring in the axial region. By dividing the near-field region into 10 sectors, the raw computation time is reduced by nearly a factor of 2 for each expression evaluated in this grid. The grid sectoring approach is most effective when the computation time is reduced without increasing the peak error, and this is consistently accomplished with the efficient integral formulation. Of the four single integral expressions evaluated with grid sectoring, the efficient formulation that eliminates redundant calculations and subtracts the singularity demonstrates the smallest computation time for a specified value of the maximum error.

Acoustics↗

Radiation forces exerted on arbitrarily located sphere by acoustic tweezer.

In a previous paper acoustic radiation force on a lipid sphere in a 100-MHz focused Gaussian field was calculated to demonstrate the acoustic tweezer effect near the focus. The theoretical formulation was based on the situation where the sphere is centered along the beam axis. Given intensity distribution independent of the x axis, it was then approximated by a cylindrical model for the sake of simplicity. Only the axial forces were considered because no lateral forces exist due to an object's symmetry. However, it was difficult to employ the same technique to the more general case when it is off the beam axis. To overcome the limitation, in this paper the previous model is modified to compute two additional lateral forces by carrying out the projection over arbitrary incident planes to restrict the integration limits. For different sizes of the sphere, the magnitudes of the net forces in three orthogonal directions are computed. The results show that the acoustic tweezer can be realized more easily in the lateral directions than in the axial directions. Differing from the axisymmetric case, the spheres of small sizes tend to be more strongly attracted than the larger ones in the lateral directions.

Acoustics↗

Stereotactic localization of breast lesions: how it works and methods to improve accuracy.

A computer simulation of stereotactic breast biopsy was developed that paralleled the geometric configuration of a currently available breast biopsy system. This model was developed to define and improve the targeting of breast lesions with stereotactic biopsy techniques. Lesions must be clearly identified and accurately targeted on both views for successful localization. Nonvisualization of a lesion may result from overlying tissue or from the geometric configuration of the imaging system. Familiarity with the geometric configuration of the biopsy unit, especially the location of the reference point and center of rotation, facilitates understanding of apparent changes in lesion position (parallax shift). Inaccuracy in lesion targeting on one or both views will manifest predominantly as an error in the calculated z value (depth). The magnitude and direction of this error are largely determined by the direction of the targeting error. Compensatory strategies include use of a long-throw core biopsy gun or directional vacuum-assisted biopsy device and additional sampling along the z axis and should be accompanied by critical evaluation of both pre- and postfire images. Understanding geometric considerations as well as how targeting accuracy affects accuracy in lesion localization should lead to greater success in sampling even challenging breast lesions at stereotactic biopsy.

Biopsy, Needle↗

Homocysteine and B vitamins relate to brain volume and white-matter changes in geriatric patients with psychiatric disorders.

OBJECTIVE: There is a growing literature on the relationship between low serum B-vitamins, elevated homocysteine, and cognitive impairment; however, few studies have examined radiological markers of associated neuropathology in geropsychiatry inpatients. The authors examined the relationship of homocysteine, folate, and vitamin B12 with magnetic resonance imaging (MRI) markers of neuropathology. METHODS: In this archival study, authors reviewed the MRIs and medical records of 34 inpatients in a geriatric psychiatry unit. Patients were selected if folate, B12, and/or homocysteine levels had been assessed and if the appropriate clinical MRIs were performed (19 men; mean age, 75 years). Patients with schizophrenia or current substance dependence were excluded. The relationships between MRI volume measures, white-matter hyperintensity (WMH) grade, and serum concentrations of folate, B12, and homocysteine were analyzed, using age-adjusted Pearson correlations. RESULTS: Homocysteine was related to WMH grade, but not brain-volume measures. Folate was associated with hippocampus and amygdala, and negatively associated with WMH. B12 level was not statistically associated with any brain measure. CONCLUSIONS: Elevated homocysteine and low folate were associated with radiological markers of neuropathology. Since no patient had clinically deficient folate, it may be important to rethink what defines functionally significant micronutrient deficiency and explore what this means in different age- and health-status groups. Larger samples will be needed to assess interactions between homocysteine, micronutrients, and other neuropathology risk factors.

Adult↗

Sex differences in brain structure in geriatric depression.

OBJECTIVE: In an exploratory study, authors compared patients with late-life major depression (MDD) and age-matched control subjects to examine sex differences in frontal and orbito-frontal (OFC) regional brain volumes. METHODS: The study sample comprised 41 patients with MDD and 41 controls. Subjects underwent comprehensive neuropsychiatric examinations and magnetic resonance imaging (MRI) scans. Corrected frontal and OFC gray-matter volumes were compared among men and women in both groups. RESULTS: The depression group had lower MMSE scores, greater severity of medical burden, apathy, psychomotor retardation, and poor health-related quality of life than the controls. Men in both groups had a greater severity of medical burden, apathy, and psychomotor retardation than women. The depression group had smaller OFC total and gray-matter volumes than the controls after matching for age. Men had smaller frontal-matter volumes than women in both groups. The diagnosis x sex interaction in brain regional volumes was observed only after controlling for medical burden. CONCLUSIONS: Sex differences in brain neuroanatomy may be important in the pathophysiology of geriatric depression. Men may be susceptible to atrophy in frontal subregions. Medical burden may contribute to the diagnosis x sex interaction in brain regional volumes.

Aged↗

Progressive brain volume loss during adolescence in childhood-onset schizophrenia.

OBJECTIVE: Previous reports have documented a striking progressive reduction in cortical gray matter volume during adolescence in patients with childhood-onset schizophrenia. This study examined the rate of loss in cortical gray matter volume in relation to age and clinical status in adolescent patients over a follow-up period of 2-6 years. METHOD: A total of 131 brain magnetic resonance imaging scans were acquired for 60 subjects with childhood-onset schizophrenia (mean age=14.5 years, SD=2.5), and 140 scans were acquired for 64 matched healthy comparison subjects. One or more follow-up scans were acquired at approximately 2-year intervals for 39 subjects with childhood-onset schizophrenia and 43 healthy subjects. Developmental trajectories for total and regional brain volumes were examined in relation to age by using polynomial growth models and data from all available scans. The rate of gray matter reduction in patients with childhood-onset schizophrenia was examined in relation to developmental and clinical measures by using stepwise regression. RESULTS: Rates of brain volume reduction were significantly higher for patients with childhood-onset schizophrenia than for healthy comparison subjects. In childhood-onset schizophrenia, the rate of gray matter reduction was related to premorbid impairment and baseline severity of clinical symptoms but not to gender, ethnicity, or age at onset of the disorder. Unexpectedly, greater clinical improvement was significantly related to a higher rate of gray matter reduction. Longitudinal trajectories suggested that the rate of cortical loss plateaus during adolescence. CONCLUSIONS: Striking loss of cerebral gray matter is seen through adolescence in patients with childhood-onset schizophrenia. The rate of reduction was related to premorbid impairment and baseline symptom severity, but it may also be in part a plastic response to illness.

Adolescent↗

Smaller anterior hippocampal formation volume in antipsychotic-naive patients with first-episode schizophrenia.

OBJECTIVE: The authors investigated volumetric alterations of the anterior hippocampal formation in patients experiencing a first episode of schizophrenia relative to healthy comparison subjects. METHOD: From contiguous 1.5-mm coronal magnetic resonance images, the hippocampal formation was divided into posterior and anterior segments, and the anterior hippocampal formation was separated from the amygdala. Volumes of the posterior and anterior hippocampal formation and amygdala were computed in 46 (31 male and 15 female) patients experiencing a first episode of schizophrenia and in 34 (21 male and 13 female) healthy comparison subjects. Twenty-four patients were antipsychotic naive at the time of the scan. RESULTS: Patients had significantly reduced total (right plus left) anterior hippocampal formation volume relative to healthy comparison subjects but did not differ in volumes of either the posterior hippocampal formation or amygdala. Similar findings were obtained when analyses were restricted to the antipsychotic-naive subgroup of patients. CONCLUSIONS: These findings suggest that volumetric abnormalities of the hippocampus-amygdala complex may be specific to the anterior hippocampal formation in patients experiencing a first episode of schizophrenia and are consistent with hypotheses regarding abnormal frontolimbic connectivity playing a role in the pathophysiology of the disorder.

Acute Disease↗

SHOWICD: a computer program to display ICD-9CM coded injury diagnoses and their corresponding injury severity scores for a particular patient.

SHOWICD is an interactive computer program designed to document severity of injury from the ICD-9CM coded injury diagnoses of a particular patient. Two severity-of-injury scores [the Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS)] are used. By employing the AIS scores, the severity of injury may be assessed per body region. The ISS provides an over-all index or summary score for severity of injury of the whole body. SHOWICD allows the user to analyze the effects of different types of injuries on the Injury Severity Score. SHOWICD may be employed either alone as a program or as a procedure in database management systems. The program is written in Turbo Pascal.

Abbreviated Injury Scale↗

Simultaneous storage of medical images in the spatial and frequency domain: a comparative study.

BACKGROUND: Digital watermarking is a technique of hiding specific identification data for copyright authentication. This technique is adapted here for interleaving patient information with medical images, to reduce storage and transmission overheads. METHODS: The patient information is encrypted before interleaving with images to ensure greater security. The bio-signals are compressed and subsequently interleaved with the image. This interleaving is carried out in the spatial domain and Frequency domain. The performance of interleaving in the spatial, Discrete Fourier Transform (DFT), Discrete Cosine Transform (DCT) and Discrete Wavelet Transform (DWT) coefficients is studied. Differential pulse code modulation (DPCM) is employed for data compression as well as encryption and results are tabulated for a specific example. RESULTS: It can be seen from results, the process does not affect the picture quality. This is attributed to the fact that the change in LSB of a pixel changes its brightness by 1 part in 256. Spatial and DFT domain interleaving gave very less %NRMSE as compared to DCT and DWT domain. CONCLUSION: The Results show that spatial domain the interleaving, the %NRMSE was less than 0.25% for 8-bit encoded pixel intensity. Among the frequency domain interleaving methods, DFT was found to be very efficient.

Algorithms↗