Retrieved cerebral thrombi studied by T2 and ADC mapping: preliminary results.

Background Recent advances in MRI technology makes it increasingly more competitive to CT also in the field of interventions. Multi-parametric MRI offers a significant amount of data relevant for characterization of human cerebral thrombi. Patients and methods Cerebral thrombi of 17 patients diagnosed with acute stroke were acquired by mechanical thrombectomy. The thrombi were subsequently scanned using a high spatial-resolution 3D T1-weighted MRI to obtain morphological characteristics of the thrombi and also by apparent diffusion coefficient (ADC) and transversal nuclear magnetic resonance (NMR) relaxation time (T2) mapping. The MRI results were analysed for possible correlations between thrombectomy procedure parameters (recanalization time and number of passes) and MR-measurable parameters (sample-mean ADC and T2, within-sample coefficient of variation of ADC and T2, and thrombus length). Results Both MRI mapping techniques enabled a good discrimination among thrombi regions of different water mobility and compaction. Within-sample coefficient of variation of ADC was found most sensitive for discrimination between the thrombi where thrombectomy procedure was performed in a single pass and those where is was performed in two or more passes (p = 0.03). Interestingly, negative correlation was found between the recanalization time and thrombus length (ρ = -0.22). Conclusions Preliminary results of presented study shows that pretreatment MRI assessment of thrombi in stroke patients could potentially ease stroke treatment planning. In this study it is shown that within-sample coefficient of variation of ADC could serve for prediction of possible complications during thrombectomy procedures.

Variable heat shock response model for medical laser procedures.

According to the standard Arrhenius relation, tissue damage is linearly dependent on the duration of exposure to elevated temperatures and exponentially dependent on the temperature itself. However, recently published measurements of damage threshold temperatures at extremely short exposure times (commonly present during laser treatments) exhibit a shift to temperatures that are higher than what would normally be expected from a single-process Arrhenius model. A novel variable heat shock (VHS) response model was developed that takes into account the observed deviation from the single-process Arrhenius relation, by assuming that the cell viability can be described as the combined effect of two biochemical processes that dominate cell survival characteristics at very short and very long exposure times. The potential implications of the VHS model are explored theoretically through an example of non-ablative laser resurfacing. The VHS model shows that under the appropriate conditions, very high temperature heat shocks can be generated within the superficial epithelium tissue layer without causing irreversible tissue damage. A mechanism of action for tissue regeneration by means of non-ablative resurfacing with the Er:YAG laser is proposed, which involves indirect triggering of tissue regeneration through intense heat shock to the epithelia, in addition to the tissue regeneration mechanism by means of direct thermal injury to deeper lying connective tissues.

Multiparametric High-Resolution MRI as a Tool for Mapping of Hypoxic Level in Tumors.

Hypoxia is a condition, common to most malignant tumors, where oxygen tension in the tissue is below the physiological level. Among consequences of tumor hypoxia is also altered cancer cell metabolism that contributes to cancer therapy resistance. Therefore, precise assessment of tumor hypoxia is important for monitoring the tumor treatment progression. In this study, we propose a simple model for prediction of hypoxic level in tumors based on multiparametric magnetic resonance imaging. The study was performed on B16F1 murine melanoma tumors ex vivo that were first magnetic resonance scanned and then analyzed for hypoxic level using hypoxia-inducable factor 1-alpha antibody staining. Each tumor was analyzed in identical sections and in identical regions of interest for pairs of hypoxic level and magnetic resonance values (apparent diffusion coefficient and T2). This was followed by correlation analysis between hypoxic level and respective magnetic resonance values. A moderate correlation was found between hypoxic level and apparent diffusion coefficient (ρ = 0.56, P < .00001) and lower between hypoxic level and T2 (ρ = 0.38, P < .00001). The data were analyzed further to obtain simple predictive models based on the multiple linear regression analysis of the measured hypoxic level (dependent variable) and apparent diffusion coefficient and T2 (independent variables). Among the hypoxic level models, the most efficient was the 3-parameter model given by relation ( HL = kADC ADC + kT2 T2 + b), where kADC = 26%/µm2/ms, kT2 = 0.8%/ms, and b = -32%. The model can be used for calculation of the predicted hypoxic level map based on magnetic resonance-measured apparent diffusion coefficient and T2 maps. Similar prediction models, based on tumor apparent diffusion coefficient and T2 maps, can be done also for other tumor types in vivo and can therefore help in assessment of tumor treatment as well as to better understand the role of hypoxia in cancer progression.

A Bond-Fluctuation Model of Translational Dynamics of Chain-like Particles through Mucosal Scaffolds.

Mucus scaffolds represent one of the most common barriers in targeted drug delivery and can remarkably reduce the outcome of pharmacological therapies. An efficient transport of drug particles through a mucus barrier is a precondition for an efficient drug delivery. Understanding the transport mechanism is particularly important for treatment of disorders such as cystic fibrosis. These are characterized by an onset of high-density mucus scaffolds imposing an increased steric filtering. In this study, we employed the bond-fluctuation model to analyze the effect of steric interactions on slowing the translational dynamics of compound chain-like particles traversing through scaffolds of different configurations (regular isotropic and anisotropic versus irregular random). The model, which accounts for both the geometry-imposed steric interaction as well as the intrachain steric interaction between the chain subunits, yields a transient subdiffusive motional pattern persists between the short-time and long-time Gaussian diffusion limits. The motion is analyzed in terms of a mean-squared displacement, diffusion coefficient, and radius of gyration. With higher levels of restriction or larger particles, the subdiffusive motional regime persists longer. The study also demonstrates that an important feature of the motion is also geometry-induced chain accommodation. The presented model is generic and could also be applied to studying the translational dynamics of other particles with more complex architecture such as dendrites or chain-decorated nanoparticles.

Predicting irreversible electroporation-induced tissue damage by means of magnetic resonance electrical impedance tomography.

Irreversible electroporation (IRE) is gaining importance in routine clinical practice for nonthermal ablation of solid tumors. For its success, it is extremely important that the coverage and exposure time of the treated tumor to the electric field is within the specified range. Measurement of electric field distribution during the electroporation treatment can be achieved using magnetic resonance electrical impedance tomography (MREIT). Here, we show improved MREIT-enabled electroporation monitoring of IRE-treated tumors by predicting IRE-ablated tumor areas during IRE of mouse tumors in vivo. The in situ prediction is enabled by coupling MREIT with a corresponding Peleg-Fermi mathematical model to obtain more informative monitoring of IRE tissue ablation by providing cell death probability in the IRE-treated tumors. This technique can potentially be used in electroporation-based clinical applications, such as IRE tissue ablation and electrochemotherapy, to improve and assure the desired treatment outcome.

Diffusion tensor MR microscopy of tissues with low diffusional anisotropy.

BACKGROUND: Diffusion tensor imaging exploits preferential diffusional motion of water molecules residing within tissue compartments for assessment of tissue structural anisotropy. However, instrumentation and post-processing errors play an important role in determination of diffusion tensor elements. In the study, several experimental factors affecting accuracy of diffusion tensor determination were analyzed. MATERIALS AND METHODS: Effects of signal-to-noise ratio and configuration of the applied diffusion-sensitizing gradients on fractional anisotropy bias were analyzed by means of numerical simulations. In addition, diffusion tensor magnetic resonance microscopy experiments were performed on a tap water phantom and bovine articular cartilage-on-bone samples to verify the simulation results. RESULTS: In both, the simulations and the experiments, the multivariate linear regression of the diffusion-tensor analysis yielded overestimated fractional anisotropy with low SNRs and with low numbers of applied diffusion-sensitizing gradients. CONCLUSIONS: An increase of the apparent fractional anisotropy due to unfavorable experimental conditions can be overcome by applying a larger number of diffusion sensitizing gradients with small values of the condition number of the transformation matrix. This is in particular relevant in magnetic resonance microscopy, where imaging gradients are high and the signal-to-noise ratio is low.

In situ monitoring of electric field distribution in mouse tumor during electroporation.

PURPOSE: To investigate the feasibility of magnetic resonance (MR) electric impedance tomography ( EIT electric impedance tomography ) technique for in situ monitoring of electric field distribution during in vivo electroporation of mouse tumors to predict reversibly electroporated tumor areas. MATERIALS AND METHODS: All experiments received institutional animal care and use committee approval. Group 1 consisted of eight tumors that were used for determination of predicted area of reversibly electroporated tumor cells with MR EIT electric impedance tomography by using a 2.35-T MR imager. In addition, T1-weighted images of tumors were acquired to determine entrapment of contrast agent within the reversibly electroporated area. A correlation between predicted reversible electroporated tumor areas as determined with MR EIT electric impedance tomography and areas of entrapped MR contrast agent was evaluated to verify the accuracy of the prediction. Group 2 consisted of seven tumors that were used for validation of radiologic imaging with histopathologic staining. Histologic analysis results were then compared with predicted reversible electroporated tumor areas from group 1. Results were analyzed with Pearson correlation analysis and one-way analysis of variance. RESULTS: Mean coverage ± standard deviation of tumors with electric field that leads to reversible electroporation of tumor cells obtained with MR EIT electric impedance tomography (38% ± 9) and mean fraction of tumors with entrapped MR contrast agent (41% ± 13) were correlated (Pearson analysis, r = 0.956, P = .005) and were not statistically different (analysis of variance, P = .11) from mean fraction of tumors from group 2 with entrapped fluorescent dye (39% ± 12). CONCLUSION: MR EIT electric impedance tomography can be used for determining electric field distribution in situ during electroporation of tissue. Implementation of MR EIT electric impedance tomography in electroporation-based applications, such as electrochemotherapy and irreversible electroporation tissue ablation, would enable corrective interventions before the end of the procedure and would additionally improve the treatment outcome.

Ex vivo and in silico feasibility study of monitoring electric field distribution in tissue during electroporation based treatments.

Magnetic resonance electrical impedance tomography (MREIT) was recently proposed for determining electric field distribution during electroporation in which cell membrane permeability is temporary increased by application of an external high electric field. The method was already successfully applied for reconstruction of electric field distribution in agar phantoms. Before the next step towards in vivo experiments is taken, monitoring of electric field distribution during electroporation of ex vivo tissue ex vivo and feasibility for its use in electroporation based treatments needed to be evaluated. Sequences of high voltage pulses were applied to chicken liver tissue in order to expose it to electric field which was measured by means of MREIT. MREIT was also evaluated for its use in electroporation based treatments by calculating electric field distribution for two regions, the tumor and the tumor-liver region, in a numerical model based on data obtained from clinical study on electrochemotherapy treatment of deep-seated tumors. Electric field distribution inside tissue was successfully measured ex vivo using MREIT and significant changes of tissue electrical conductivity were observed in the region of the highest electric field. A good agreement was obtained between the electric field distribution obtained by MREIT and the actual electric field distribution in evaluated regions of a numerical model, suggesting that implementation of MREIT could thus enable efficient detection of areas with insufficient electric field coverage during electroporation based treatments, thus assuring the effectiveness of the treatment.