John D. Hazle

Modulation of in Vivo Tumor Radiation Response via Gold Nanoshell-Mediated Vascular-Focused Hyperthermia: Characterizing an Integrated Antihypoxic and Localized Vascular Disrupting Targeting Strategy

We report noninvasive modulation of in vivo tumor radiation response using gold nanoshells. Mild-temperature hyperthermia generated by near-infrared illumination of gold nanoshell-laden tumors, noninvasively quantified by magnetic resonance temperature imaging, causes an early increase in tumor perfusion that reduces the hypoxic fraction of tumors. A subsequent radiation dose induces vascular disruption with extensive tumor necrosis. Gold nanoshells sequestered in the perivascular space mediate these two tumor vasculature-focused effects to improve radiation response of tumors. This novel integrated antihypoxic and localized vascular disrupting therapy can potentially be combined with other conventional antitumor therapies.

Histopathologic correlation of magnetic resonance imaging signal patterns in a spinal cord injury model

Magnetic resonance imaging (MRI) provides a noninvasive method of monitoring the pathologic response to spinal cord injury. Specific MR signal intensity patterns appear to correlate with degrees of improvement in the neurologic status in spinal cord injury patients. Histologic correlation of two types of MR signal intensity patterns are confirmed in the current study using a rat animal model. Adult male Sprague-Dawley rats underwent spinal cord trauma at the midthoracic level using a weight-dropping technique. After laminectomy, 5- and 10-gm brass weights were dropped from designated heights onto a 0.1-gm impounder placed on the exposed dura. Animals allowed to regain consciousness demonstrated variable recovery of hind limb paraplegia. Magnetic resonance images were obtained from 2 hours to 1 week after injury using a 2-tesla MRI/spectrometer. Sacrifice under anesthesia was performed by perfusive fixation; spinal columns were excised en bloc, embedded, sectioned, and observed with the compound light microscope. Magnetic resonance axial images obtained during the time sequence after injury demonstrate a distinct correlation between MR signal intensity patterns and the histologic appearance of the spinal cord. Magnetic resonance imaging delineates the pathologic processes resulting from acute spinal cord injury and can be used to differentiate the type of injury and prognosis.

Magnetic resonance imaging-guided focused ultrasound thermal therapy in experimental animal models: Correlation of ablation volumes with pathology in rabbit muscle and VX2 tumors

To further investigate the use of magnetic resonance‐guided focused ultrasound therapy (MRgFUS) as a noninvasive alternative to surgery in the local control of soft‐tissue tumors by ablating prescribed volumes of VX2 rabbit tumors and comparing with ablation of normal tissue volumes.

Fat-suppressed three-dimensional dual echo Dixon technique for contrast agent enhanced MRI.

To develop a fast T1‐weighted, fat‐suppressed three‐dimensional dual echo Dixon technique and to demonstrate its use in contrast agent enhanced MRI.

Laser‐induced thermal response and characterization of nanoparticles for cancer treatment using magnetic resonance thermal imaging

Spherical nanoparticles with a gold outer shell and silica core can be tuned to absorb near-infrared light of a specific wavelength. These nanoparticles have the potential to enhance the treatment efficacy of laser-induced thermal therapy (LITT). In order to enhance both the potential efficacy and safety of such procedures, accurate methods of treatment planning are needed to predict the temperature distribution associated with treatment application. In this work, the standard diffusion approximation was used to model the laser fluence in phantoms containing different concentrations of nanoparticles, and the temperature distribution within the phantom was simulated in three-dimensions using the finite element technique. Magnetic resonance temperature imaging was used to visualize the spatiotemporal distribution of the temperature in the phantoms. In most cases, excellent correlation is demonstrated between the simulations and the experiment (<3.0% mean error observed). This has significant implications for the treatment planning of LITT treatments using gold-silica nanoshells.

Design and performance characteristics of a digital flat-panel computed tomography system

Computed tomography (CT) applications continue to expand, and they require faster data acquisition speeds and improved spatial resolution. Achieving isotropic resolution, by means of cubic voxels, in combination with longitudinal coverage beyond 20 mm would represent a substantial advance in clinical CT because few commercially available scanners are capable of this at present. To achieve this goal, a prototype CT system incorporating a movable array of 20 cm X 20 cm, 200-microm-pitch amorphous silicon flat-panel x-ray detectors and a conventional CT x-ray source was constructed at the General Electric Global Research Center and performance tested at The University of Texas M. D. Anderson Cancer Center. The device was designed for preclinical imaging applications and has a scan field of 13 to 33 cm, with a magnification of 1.5. Image quality performance measurements, such as spatial and contrast resolutions, were obtained using both industry standard and custom phantoms. Spatial resolution, quantified by the systems modulation transfer function, indicated improvement by a factor of 2.5 to 5 in isotropic spatial resolution over current commercially available systems, with 10% modulation transfer function modulations at frequencies from 19 to 31 lp/cm. Low-contrast detectability results were obtained from industry-standard phantoms and were comprised of embedded contrast regions of 0.3%, 0.5%, and 1.0% over areas of several mm2. Performance was sufficient to easily distinguish 1.0% contrast regions down to 2 mm in diameter relative to the background. On the basis of scans of specialized hydroxyapatite phantoms, the system response is extremely linear (R2=0.990) in bone-equivalent density regimens. Standard CT dose index CTDI100 and CTDIw measurements were also conducted to assess dose delivery using a 16-cm-CTDI phantom and a 120 kV 120 mAs scan technique. The CTDIw ranged from 30 mGy (one-panel mode) to 113 mGy (two-panel mode) for this system. Lastly, several in vivo canine and murine samples were examined, and preliminary results from these scans are presented. On the basis of our results, it is clear that flat-panel-based CT scanners are useful for high-contrast high-resolution clinical applications, providing up to a 20-fold increase in volumetric resolution over most commercially available scanners.

Partially parallel imaging with phase-sensitive data: Increased temporal resolution for magnetic resonance temperature imaging.

Magnetic resonance temperature imaging can be used to monitor the progress of thermal ablation therapies, increasing treatment efficacy and improving patient safety. High temporal resolution is important when therapies rapidly heat tissue, but many approaches to faster image acquisition compromise image resolution, slice coverage, or phase sensitivity. Partially parallel imaging techniques offer the potential for improved temporal resolution without forcing such concessions. Although these techniques perturb image phase, relative phase changes between dynamically acquired phase‐sensitive images, such as those acquired for MR temperature imaging, can be reliably measured through partially parallel imaging techniques using reconstruction filters that remain constant across the series. Partially parallel and non‐accelerated phase‐difference‐sensitive data can be obtained through arrays of surface coils using this method. Average phase differences measured through partially parallel and fully Fourier encoded images are virtually identical, while phase noise increases with g

Use of gold nanoshells to constrain and enhance laser thermal therapy of metastatic liver tumours.

sqrt{rm L}

Quantitative comparison of thermal dose models in normal canine brain

as in standard partially parallel image acquisitions. Magn Reson Med 53:658–665, 2005.

Specimen Radiography in Confirmation of MRI-Guided Needle Localization and Surgical Excision of Breast Lesions

Purpose: To investigate the impact of intravenously injected gold nanoparticles on interstitially delivered laser induced thermal therapy (LITT) in the liver. Methods: 3D finite element modelling, ex vivo canine liver tissue containing gold nanoparticles absorbing at 800 nm, and agar gel phantoms were used to simulate the presence of nanoparticles in the liver during LITT. Real-time magnetic resonance temperature imaging (MRTI) based on the temperature sensitivity of the proton resonance frequency shift (PRFS) was used to map the spatiotemporal distribution of heating in the experiments and validate the predictions of 3D finite element simulations of heating. Results: Experimental results show good agreement with both the simulation and the ex vivo experiments. Average discrepancy between simulation and experiment was shown to be 1.6°C or less with the maximum difference being 3.8°C due to a small offset in laser positioning. Conclusion: A high nanoshell concentration in the surrounding liver parenchyma, such as that which would be expected from an intravenous injection of gold nanoshells (∼120 nm) acts as both a beam stop for the laser and secondary heat source for the treatment, helping to better heat the lesions and confine the treatment to the lesion. This indicates a potential to use nanoparticles to enhance both the safety and efficacy of LITT procedures in the liver.