Biomechanical properties of the hypoxic and dying brain quantified by magnetic resonance elastography.

Respiratory arrest is a major life-threatening condition leading to cessation of vital functions and hypoxic-anoxic injury of the brain. The progressive structural tissue changes characterizing the dying brain biophysically are unknown. Here we use noninvasive magnetic resonance elastography to show that biomechanical tissue properties are highly sensitive to alterations in the brain in the critical period before death. Our findings demonstrate that brain stiffness increases after respiratory arrest even when cardiac function is still preserved. Within 5 min of cardiac arrest, cerebral stiffness further increases by up to 30%. This early mechanical signature of the dying brain can be explained by water accumulation and redistribution from extracellular spaces into cells. These processes, together, increase interstitial and intracellular pressure as revealed by magnetic resonance spectroscopy and diffusion-weighted imaging. Our data suggest that the fast response of cerebral stiffness to respiratory arrest enables the monitoring of life-threatening brain pathology using noninvasive in vivo imaging. STATEMENT OF SIGNIFICANCE: Hypoxia-anoxia is a life-threatening condition eventually leading to brain death. Therefore, monitoring vital brain functions in patients at risk is urgently required during emergency care or treatment of acute brain damage due to insufficient oxygen supply. In mouse model of hypoxia-anoxia, we have shown for the first time that biophysical tissue parameters such as brain stiffness changed markedly during the process of death.

Sensitivity of multifrequency magnetic resonance elastography and diffusion-weighted imaging to cellular and stromal integrity of liver tissue.

Microscopic structural alterations of liver tissue induced by freeze-thaw cycles give rise to palpable property changes. However, the underlying damage to tissue architecture is difficult to quantify histologically, and published data on macroscopic changes in biophysical properties are sparse. To better understand the influence of hepatic cells and stroma on global biophysical parameters, we studied rat liver specimens freshly taken (within 30 min after death) and treated by freeze-thaw cycles overnight at either -20 °C or -80 °C using diffusion-weighted imaging (DWI) and multifrequency magnetic resonance elastography (MRE) performed at 0.5 T in a tabletop MRE scanner. Tissue structure was analyzed histologically and rheologic data were analyzed using fractional order derivatives conceptualized by a called spring-pot component that interpolates between pure elastic and viscous responses. Overnight freezing and thawing induced membrane disruptions and cell detachment in the space of Disse, resulting in a markedly lower shear modulus µ and apparent diffusion coefficient (ADC) (µ[-20 °C] = 1.23 ±â€¯0.73 kPa, µ[-80 °C] = 0.66 ±â€¯0.75 kPa; ADC[-20 °C] = 0.649 ±â€¯0.028 µm2/s, ADC[-80 °C] = 0.626 ±â€¯0.025 µm2/s) compared to normal tissue (µâ€¯= 9.92 ±â€¯3.30 kPa, ADC = 0.770 ±â€¯0.023 µm2/s, all p < 0.001). Furthermore, we analyzed the springpot-powerlaw coefficient and observed a reduction in -20 °C specimens (0.22 ±â€¯0.14) compared to native tissue (0.40 ±â€¯0.10, p = 0.033) and -80 °C specimens (0.54 ±â€¯0.22, p = 0.002), that correlated with histological observations of sinusoidal dilation and collagen distortion within the space of Disse. Overall, the results suggest that shear modulus and water diffusion in liver tissue markedly decrease due to cell membrane degradation and cell detachment while viscosity-related properties appear to be more sensitive to distorted stromal and microvascular architecture.

Synthesis of europium-doped VSOP, customized enhancer solution and improved microscopy fluorescence methodology for unambiguous histological detection.

BACKGROUND: Intrinsic iron in biological tissues frequently precludes unambiguous the identification of iron oxide nanoparticles when iron-based detection methods are used. Here we report the full methodology for synthesizing very small iron oxide nanoparticles (VSOP) doped with europium (Eu) in their iron oxide core (Eu-VSOP) and their unambiguous qualitative and quantitative detection by fluorescence. METHODS AND RESULTS: The resulting Eu-VSOP contained 0.7 to 2.7% Eu relative to iron, which was sufficient for fluorescent detection while not altering other important particle parameters such as size, surface charge, or relaxivity. A customized enhancer solution with high buffer capacity and nearly neutral pH was developed to provide an antenna system that allowed fluorescent detection of Eu-VSOP in cells and histologic tissue slices as well as in solutions even under acidic conditions as frequently obtained from dissolved organic material. This enhancer solution allowed detection of Eu-VSOP using a standard fluorescence spectrophotometer and a fluorescence microscope equipped with a custom filter set with an excitation wavelength (λex) of 338 nm and an emission wavelength (λem) of 616 nm. CONCLUSION: The fluorescent detection of Eu-doped very small iron oxide nanoparticles (Eu-VSOP) provides a straightforward tool to unambiguously characterize VSOP biodistribution and toxicology at tissue, and cellular levels, providing a sensitive analytical tool to detect Eu-doped IONP in dissolved organ tissue and biological fluids with fluorescence instruments.