Annals of biomedical engineering
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Solid tumors and other pathologies can be treated using laser thermal ablation under interventional magnetic resonance imaging (iMRI) guidance. A model was developed to predict cell death from magnetic resonance (MR) thermometry measurements based on the temperature-time history, and validated using in vivo rabbit brain data. To align post-ablation T2-weighted spin-echo MR lesion images to gradient-echo MR images, from which temperature is derived, a registration method was used that aligned fiducials placed near the thermal lesion. ⋯ Mislabeled voxels were typically within one voxel from the segmented necrotic boundary with median distances of 0.77 and 0.22 mm for false positives (FP) and false negatives (FN), respectively. As compared to the critical temperature cell death model and the generalized Arrhenius model, our model typically predicted fewer FP and FN. This is good evidence that iMRI temperature maps can be used with our model to predict therapeutic regions in real-time during treatment.
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In recent years, development of rheumatoid arthritis (RA) drug therapy has been more directly targeted to counteract specific mechanisms of inflammation, and it is now believed that early aggressive treatment with disease modifying drugs is important to inhibit future structural joint damage. The development of these new treatments has increased the need for methodologies to assess disease activity in RA and monitor the effectiveness of drug therapy. Unlike X-ray, which shows only structural bone damage, magnetic resonance imaging (MRI) can depict soft tissue damage and synovitis, the primary pathology of RA. ⋯ Preliminary results show good correlation to early enhancement rate, which has previously been shown to be a useful clinical marker of RA activity. However, the use of tracer kinetic modeling methods potentially provides more specific information regarding underlying RA physiology. This approach could provide a useful new tool in RA patient management and could substantially improve RA therapeutic studies by calculating objective biomarkers of the disease state.
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In vitro models of brain injury that use thick 3-D cultures and control extracellular matrix constituents allow evaluation of cell-matrix interactions in a more physiologically relevant configuration than traditional 2-D cultures. We have developed a 3-D cell culture system consisting of primary rat cortical neurons distributed throughout thick (>500 microm) gels consisting of type IV collagen (Col) conjugated to agarose. Neuronal viability and neurite outgrowth were examined for a range of agarose (AG) percentages (1.0-3.0%) and initial collagen concentrations ([Col](i); 0-600 microg/mL). ⋯ Following high rate deformation, neuronal viability significantly decreased with increasing [Col](i), implicating cell-matrix adhesions in acute mechanotransduction events associated with traumatic loading. These results suggest interrelated roles for matrix mechanical properties and receptor-mediated cell-matrix interactions in neuronal viability, neurite outgrowth, and transduction of high rate deformation. This model system may be further exploited for the elucidation of mechanotransduction mechanisms and cellular pathology following mechanical insult.
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A novel approach for detection of polynomial nonlinearity in the neuro-cardiovascular system based on cyclostationary analysis is presented. Metronome breathing is employed to provide a sinusoidal input to the neuro-cardiovascular system in which Heart Rate Variability (HRV) and Blood Pressure Variation (BPV) are considered as its outputs. ⋯ It is shown that a second order polynomial nonlinear system is actually involved in producing the HRV and BPV. The strength of this nonlinearity decreases with increasing the breathing rate.
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The objective of our work has been to investigate the use of ultrasound image-guided high-intensity focused ultrasound (HIFU) to non-invasively produce conduction block in rabbit sciatic nerves in vivo, a technique that could become a treatment of spasticity and pain. The work reported here involved the investigation of the duration of such conduction blocks after HIFU treatment and whether they resulted in axon degeneration. The right sciatic nerves of 12 rabbits were treated, under guidance of ultrasound imaging, with repeated 5-s applications of 3.2 MHz HIFU with in situ intensity of 1930 W/cm(2) (spatial-average, temporal-average) until conduction block was achieved. ⋯ The volume of necrosis of adjacent muscle was measured to be 1.59+/-1.1 cm(3) (mean+/-SD). For all nerves, conduction block remained at the survival endpoint and the block resulted in degeneration of axons distal to the HIFU site, as confirmed by electrophysiological and histological methods. Potential clinical applications include treatment of spasticity in patients with spinal cord injury or pain in cancer patients.