Wilson Miller

Quantification of regional lung ventilation from tagged hyperpolarized helium-3 MRI

In this paper we propose a new scheme for measuring regional ventilation from tagged hyperpolarized helium-3 MR images. A new registration cost function that incorporates both the intensity information (SSD) and the shape feature (SSBMD) from the images is proposed for registering end inspiration to the end expiration image. The smoothness of the displacement field is maintained by incorporating the Laplacian regularization constraint (LAP) in the total cost function. The ventilation is quantified using the Jacobian determinant of the resulting displacement field from the proposed registration algorithm. Tags are automatically segmented from the images to evaluate the registration accuracy. The average tag positioning error is on the order of 2 mm after registration for all three subjects. These results may provide new method for assessing regional lung ventilation and may be used to track regional function changes of lung cancer patients following radiation therapy.

Defining the Optimal Age for Focal Lesioning in a Rat Model of Transcranial HIFU

This study aimed at determining the optimal age group for high-intensity focused ultrasound (HIFU) experiments for producing lesions in rats. Younger rats have thinner skulls, allowing for the acoustic waves to propagate easily through the skull without causing burns of the skin and brain surface. Younger rats however, have a smaller brain that can make HIFU focusing in the brain parenchyma challenging because of the focus size. In this study, we conducted transcranial HIFU sonications in rat pups of different ages (from 9 to 43 d) with a 1.5MHz MR compatible transducer. The electric power was selected to always reach a target temperature of at least 50°C in the parenchyma. The thickness of the skull and of the brain parenchyma was measured using T2-weighted MR imaging. Results showed that the thickness of the brain parenchyma increased quickly from P9 to P12, reaching 8.5 mm at P16, and then increasing gradually along with age. The skull thickness increased gradually from P9 to P26, and then more quickly after P30. The ratio between brain parenchyma thickness and skull thickness decreased gradually with age. For the pups at 30 d, the temperature in the brain tissue adjacent to the skull increased to 48.9°C, and those from the rodents older than 33 d reached 60°C or higher, which can produce undesired irreversible damage in this location. We conclude that young rats aged 16-26 d are optimal for experiments producing transcranial HIFU lesions in rats with an intact skull.

Ultrasound-mediated delivery of brain-penetrating nanoparticles across the blood-tumor barrier

The intact blood-brain barrier (BBB) presents a major obstacle for drug delivery to the brain. In addition, both high interstitial pressure and a nanoporous electrostatically charged tissue composition, produce a “blood-tumor barrier” (BTB), further complicating the treatment of diseases like glioblastoma. Focused ultrasound (FUS) in conjunction with microbubbles (MB) has been shown to cause reversible, localized disruption of the BBB. Incorporating MR guidance with FUS offers the ability to exquisitely target the BBB disruption to specific regions of the brain, thereby permitting drug delivery in a highly localized manner. This work examines the ability of MR guided FUS to deliver highly specialized brain-penetrating nanoparticles (NP) across both the BBB and the BTB in tumor-bearing rats. NPs were 60 nm in diameter and covered with an exceptionally dense brush layer of PEG to permit excellent diffusion through brain tissue. Initial studies utilized fluorescent polystyrene tracer particles to measure NP delivery and inform dosing of cisplatin-loaded biodegradable NPs.

Correlation of measures of regional lung ventilation from 4DCT vs. hyperpolarized helium-3 MR

Radiation induced pulmonary diseases can change the tissue material properties of lung parenchyma and the mechanics of the respiratory system. Recent advances in multi-detector-row CT (MDCT), 4DCT respiratory gating methods, and image processing techniques enable us to follow and measure those changes noninvasively during radiation therapy at a regional level. This study compares the 4DCT based ventilation measurement with the results from hyperpolarized helium-3 MR using the cumulative distribution function maps and the relative overlap (RO) statistic. We show that the similarity between the two measurements increases as the increase of the B-Spline grid spacing and Laplacian weighting which result a smoother ventilation map. The best similarity is found with weighting of 0.5 for linear elasticity and B-Spline grid spacing of 32 mm. Future work is to improve the lung image registration algorithm by incorporating hyperpolarized helium-3 MR information so as to improve its physiological modeling of the lung tissue deformation.

Expanding the treatment envelope for brain therapy: simulation models and head phantoms

Thermal therapy is currently limited to central areas of the brain in order to maximize the antenna gain between the outer cortex and the target. So far, clinical applications have been limited to thalamotomies for neuropathic pain, essential tremor and Parkinsonian tremor. We developed numerical simulations and head phantoms in order to investigate the possibility to target more eccentric targets in the brain in silico and in vitro.

Accelerated MR thermometry using the Kalman filter

Magnetic resonance (MR) imaging plays an important role in monitoring thermal treatment. It can quantify thermal dose with temperature maps based on the proton-resonance frequency shift. Volumetric coverage is desirable, but acquiring multiple slices imaging is time consuming. Therefore, accelerated methods are needed to improve the spatial and temporal resolution in MR thermometry. Multi-channel coils are not widely available for MR-guided FUS systems, so conventional parallel imaging methods cannot be used for acceleration. Compressed sensing methods show promise, but the computation is currently too slow to provide real-time feedback. The Kalman filter is an optimal estimation method that has been widely used for real-time tracking in other fields. It has been studied for filtering of temperature for FUS. Here we apply it to accelerate image acquisition for thermometry.

Direct nanodroplet and microbubble comparison for high intensity focused ultrasound ablation enhancement and safety

High intensity focused ultrasound (HIFU) surgery often requires hours of ablation in order to treat an entire tumor. Both perfluorocarbon gaseous microbubbles and vaporized liquid droplets are known enhancers of HIFU thermal ablation. Microbubbles, however, often lead to surface or skin lesions. Furthermore, they have a relatively short half-life in vivo (minutes) rendering them insufficiently stable for an entire HIFU surgery, which can last several hours. Many droplet formulations require very high pressures to activate. Our aim was to design an agent that could shorten ablation procedures without sacrificing safety. We designed and investigated a perfluorocarbon nanodroplet composed of a 1:1 ratio of dodecafluoropentane and decafluorobutane. These are tuned to change phase and activate at only 2 MPa peak negative pressure with common HIFU pulse lengths, enabling focused and targeted activation. Additionally, they are stable at body temperature.

Ultrashort echo-time MRI as a substitute to CT for skull aberration correction in transcranial focused ultrasound: in vitro comparison on human calvaria

Clinical transcranial MR-guided focused ultrasound (TcMRgFUS) brain treatment systems compensate for skull-induced beam aberrations by adjusting the phase and amplitude of individual ultrasound transducer elements. These corrections are currently calculated based on a pre-acquired CT scan of the patient’s head. The purpose of the work presented here is to demonstrate the feasibility of using ultrashort echo-time (UTE) MRI instead of CT to calculate and apply aberration corrections on a clinical TcMRgFUS system.

MR bone imaging

Bone is highly relevant to focused ultrasound therapy, both as a potential treatment target and because it interferes with treatment of other organs such as the brain. It is challenging to image cortical bone using MRI, however, due to low water density and fast signal decay in bony tissues. Ultrashort echo time (UTE) imaging is a specialized MR technique that allows the weak, short-lived signal from cortical bone to be imaged despite these limitations. Potential applications of UTE bone imaging in MR-guided focused ultrasound include direct MR thermometry of bone heating, which is not possible using standard proton resonance shift (PRFS) techniques, and in situ skull imaging during brain treatment procedures, which could replace the separate CT scan currently required for transcranial focused ultrasound.