The transmission of ultrasound (US) through the skull bone has been investigated for therapeutic applications (e.g., thermal ablation of intracranial tumors and localized blood-brain-barrier disruption for drug delivery) and imaging applications (e.g., tomographic echoencephalography and brainstem monitoring for the diagnosis of Parkinson's disease). The clinical efficacy of transcranial US has been limited by the highly attenuating properties of skull bone. Diagnostic application remains limited to the pediatric population (developing bone is more transparent to US; also, transfontanelle approaches are not hindered by skull the skull bone) and to those areas within the cranial vault accessible by insonation through the temporal acoustic window. For high-intensity focused US therapy, the skull bone absorbs acoustic energy readily and the resulting heating effects pose potentially detrimental hazards for the cerebral cortex. The ability to pre-procedurally determine those areas of the skull that are less attenuating to US could be a tremendous asset for improving diagnostic and therapeutic applications of US in the brain. To present a possible solution, we hypothesize that the photon transmission intensity as related to the measured photon reflection intensity at points across the skull surface can be correlated with the local US transmission efficiency. To test this hypothesis, the proposed study will involve a statistical investigation of the relationship between backscattered photon intensity and US transmission through the skull bone. Data will be collected over multiple points across several ex vivo human calvarium specimens for analysis. This study will involve benchtop experimentation with US transducers, laser diodes, and specialized instrumentation; computer-based image processing; and the use of human ex vivo calvarium specimens.

During image-guided brain surgery, especially those which involve the resection of large masses, intraoperative brain shift renders pre-operative images unsuitable for guidance because the imagery no longer accurately represents the actual anatomical geometry. Intraoperative ultrasound has been considered as a potential modality for tracking brain shift in real-time during surgery. A novel aspect of our method is the transmission of ultrasound through the intact skull bone, away from the surgical site. In this way, the monitoring can be performed with minimal procedural interference. To improve the signal-to-noise ratio of the ultrasound signal, which passes through highly attenuating skull bone, we propose the use of a passive ultrasound detector coupled to the patient’s outer eyelid. In this way, the ultrasound signal will only be attenuated by thick skull bone in the transmit phase, and upon scattering and detection, only be subject to the less-attenuating retro-orbital bone. This layer of bone behind the orbit is more transparent to ultrasound for three reasons: (1) it is thin, (2) it is composed of only dense cortical bone, and (3) its geometry is such that most signals emanating from within the cranial vault traverse the bone at a highly oblique angle, and so transmits via the better impedance-matched shear mode. This proposed method for tracking objects within the cranial cavity will be tested by benchtop experimentation with specialized ultrasound transducers and ex vivo human skull specimens. Image analysis techniques will be designed to analyze and compare multiple methods of intracranial monitoring, with the expectation that the proposed transcranial-transorbital method will yield results that could be effectively applied in the operating room.

The transmission of ultrasound (US) through the skull bone has been investigated for therapeutic and imaging applications. One of the primary obstacles to the effective application of transcranial US is bone-induced phase aberration due to geometric variations both within a subject and between subjects. The predictability of the transmitted US wavefield within the cranial vault is paramount to the development of clinically useful US-based procedures ranging from intracranial tumor ablation and drug delivery to intraoperative monitoring and hemorrhage detection. The present gold standard for assessing skull thickness for US phase aberration correction is x-ray computed tomography (CT). Because CT has several inherent limitations as compared to US (e.g., safety, cost, and convenience), there is an interest in US-based methods for skull thickness prediction. The proposed study will investigate the potential for using US-derived data to perform aberration correction for the transcranial propagation of US. Specific details pertaining to human skull geometry will be statistically analyzed to formulate a framework by which US-based measurements will yield comparable aberration correction as CT measurements. This study will involve benchtop experimentation with US transducers and specialized instrumentation; computer-based image processing (US and CT); and the use of human ex vivo calvarium specimens.

Rapid developments in brain imaging within the past few decades have yielded numerous modalities and tools for enhancing our understanding of normal and pathological brain anatomy. Some of these modalities include x-ray computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US). As these tools have become more readily available for clinicians and researchers, it has been suggested that the combined use of multiple radiological modalities, whether in situ or synergized post-procedurally, can yield tremendous benefits in both research and clinical settings. The development of radiological tools requires the use of phantom materials that mimic the behavior of human tissues in response to the specific radiological modality being studied. Our lab, as a highly interdisciplinary research environment, incorporates numerous imaging modalities into our investigations and as such, is interested in the development of an anatomically-accurate human brain phantom that can respond in a brain tissue-like fashion to x-ray irradiation, MRI imaging, and ultrasound. In addition, as part of a larger study to investigate the use of ultrasound for thermal ablation of intracranial tumors, the multiple-modality brain phantom should also absorb and dissipate thermal energy in a fashion similar to the human brain. This study will involve benchtop experimentation (including measurements with CT scanners, MRI scanners, US transducers, and other specialized instrumentation) and computer-based image processing (CT, MRI, and US).