Histology to 3D in vivo MR registration for volumetric evaluation of MRgFUS treatment assessment biomarkers.

Advances in imaging and early cancer detection have increased interest in magnetic resonance (MR) guided focused ultrasound (MRgFUS) technologies for cancer treatment. MRgFUS ablation treatments could reduce surgical risks, preserve organ tissue and function, and improve patient quality of life. However, surgical resection and histological analysis remain the gold standard to assess cancer treatment response. For non-invasive ablation therapies such as MRgFUS, the treatment response must be determined through MR imaging biomarkers. However, current MR biomarkers are inconclusive and have not been rigorously evaluated against histology via accurate registration. Existing registration methods rely on anatomical features to directly register in vivo MR and histology. For MRgFUS applications in anatomies such as liver, kidney, or breast, anatomical features that are not caused by the treatment are often insufficient to drive direct registration. We present a novel MR to histology registration workflow that utilizes intermediate imaging and does not rely on anatomical MR features being visible in histology. The presented workflow yields an overall registration accuracy of 1.00 ± 0.13 mm. The developed registration pipeline is used to evaluate a common MRgFUS treatment assessment biomarker against histology. Evaluating MR biomarkers against histology using this registration pipeline will facilitate validating novel MRgFUS biomarkers to improve treatment assessment without surgical intervention. While the presented registration technique has been evaluated in a MRgFUS ablation treatment model, this technique could be potentially applied in any tissue to evaluate a variety of therapeutic options.

Validation of hybrid angular spectrum acoustic and thermal modelling in phantoms.

In focused ultrasound (FUS) thermal ablation of diseased tissue, acoustic beam and thermal simulations enable treatment planning and optimization. In this study, a treatment-planning methodology that uses the hybrid angular spectrum (HAS) method and the Pennes' bioheat equation (PBHE) is experimentally validated in homogeneous tissue-mimicking phantoms. Simulated three-dimensional temperature profiles are compared to volumetric MR thermometry imaging (MRTI) of FUS sonications in the phantoms, whose acoustic and thermal properties are independently measured. Additionally, Monte Carlo (MC) uncertainty analysis is performed to quantify the effect of tissue property uncertainties on simulation results. The mean error between simulated and experimental spatiotemporal peak temperature rise was +0.33°C (+6.9%). Despite this error, the experimental temperature rise fell within the expected uncertainty of the simulation, as determined by the MC analysis. The average errors of the simulated transverse and longitudinal full width half maximum (FWHM) of the profiles were -1.9% and 7.5%, respectively. A linear regression and local sensitivity analysis revealed that simulated temperature amplitude is more sensitive to uncertainties in simulation inputs than in the profile width and shape. Acoustic power, acoustic attenuation and thermal conductivity had the greatest impact on peak temperature rise uncertainty; thermal conductivity and volumetric heat capacity had the greatest impact on FWHM uncertainty. This study validates that using the HAS and PBHE method can adequately predict temperature profiles from single sonications in homogeneous media. Further, it informs the need to accurately measure or predict patient-specific properties for improved treatment planning of ablative FUS surgeries.

Development and validation of a MRgHIFU non-invasive tissue acoustic property estimation technique.

MR-guided high-intensity focussed ultrasound (MRgHIFU) non-invasive ablative surgeries have advanced into clinical trials for treating many pathologies and cancers. A remaining challenge of these surgeries is accurately planning and monitoring tissue heating in the face of patient-specific and dynamic acoustic properties of tissues. Currently, non-invasive measurements of acoustic properties have not been implemented in MRgHIFU treatment planning and monitoring procedures. This methods-driven study presents a technique using MR temperature imaging (MRTI) during low-temperature HIFU sonications to non-invasively estimate sample-specific acoustic absorption and speed of sound values in tissue-mimicking phantoms. Using measured thermal properties, specific absorption rate (SAR) patterns are calculated from the MRTI data and compared to simulated SAR patterns iteratively generated via the Hybrid Angular Spectrum (HAS) method. Once the error between the simulated and measured patterns is minimised, the estimated acoustic property values are compared to the true phantom values obtained via an independent technique. The estimated values are then used to simulate temperature profiles in the phantoms, and compared to experimental temperature profiles. This study demonstrates that trends in acoustic absorption and speed of sound can be non-invasively estimated with average errors of 21% and 1%, respectively. Additionally, temperature predictions using the estimated properties on average match within 1.2 °C of the experimental peak temperature rises in the phantoms. The positive results achieved in tissue-mimicking phantoms presented in this study indicate that this technique may be extended to in vivo applications, improving HIFU sonication temperature rise predictions and treatment assessment.

Patterning N-type and S-type neuroblastoma cells with Pluronic F108 and ECM proteins.

Influencing cell shape using micropatterned substrates affects cell behaviors, such as proliferation and apoptosis. Cell shape may also affect these behaviors in human neuroblastoma (NBL) cancer, but to date, no substrate design has effectively patterned multiple clinically important human NBL lines. In this study, we investigated whether Pluronic F108 was an effective antiadhesive coating for human NBL cells and whether it would localize three NBL lines to adhesive regions of tissue culture plastic or collagen I on substrate patterns. The adhesion and patterning of an S-type line, SH-EP, and two N-type lines, SH-SY5Y and IMR-32, were tested. In adhesion assays, F108 deterred NBL adhesion equally as well as two antiadhesive organofunctional silanes and far better than bovine serum albumin. Patterned stripes of F108 restricted all three human NBL lines to adhesive stripes of tissue culture plastic. We then investigated four schemes of applying collagen and F108 to different regions of a substrate. Contact with collagen obliterates the ability of F108 to deter NBL adhesion, limiting how both materials can be applied to substrates to produce high fidelity NBL patterning. This patterned substrate design should facilitate investigations of the role of cell shape in NBL cell behavior.