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Leukemia commonly leads to hypoxia in the bone marrow, which can then result in increased resistance to chemotherapy. However, the relationship between local hypoxia and disease progression is not well understood, and it is unclear whether hypoxia in the bone marrow is diffuse or focal in presentation. Spectroscopic photoacoustic (PA) imaging-based estimation of blood oxygen saturation (SO2) can be...
For many diseases, such as cancer, simultaneous imaging of different targets can lead to improved diagnosis, better patient prognosis, and therapy guidance/monitoring. PET-CT multiplexing can be cumbersome, costly, and involve radiation exposure. Other modalities such as fluorescent imaging lack clinical and pre-clinical relevance. Therefore, clinically relevant multiplexed imaging is of interest...
Rodents are used extensively in research to study disease and evaluate drugs. Preclinical imaging systems allow for non-invasive assessments of animals. High frequency ultrasound systems have emerged over the last 15 years as valuable tools for evaluating numerous diseases and organs. When compared against other anatomical imaging systems, such as MRI and CT, ultrasound is the most cost effective,...
Pancreatic ductal adenocarcinoma (PDA) is one of the most prevalent types of cancer. Studies have shown that PDA treatment with IV administration of gemcitabine (GEM) is inhibited by excessive interstitium and connective tissue (stroma) surrounding the tumor. Ultrasound (US) irradiation combined with drug-loaded polylactic acid (PLA) microbubble contrast agents (MB) may circumvent this through targeted...
Recently, ultrafast Doppler techniques have been proposed for imaging brain and other slow flow targets. These techniques rely on synthetic focusing and the use of large ensemble lengths to separate slow-flow signal from the stationary clutter, but are susceptible to high acoustic and thermal noise. We have recently developed the short-lag angular coherence (SLAC) method, which suppresses the incoherent...
Current liver cancer ablation methods are mainly thermal-based and inherently exhibit inconsistent tissue ablation due to irregular heat dissipation. Histotripsy is a non-thermal ultrasound (US) ablation method that fractionates tissue through the precise control of acoustic cavitation. This paper studies the feasibility and chronic effects of non-invasive histotripsy for liver cancer ablation in...
The BRICHOS domain is encoded in more than 30 genes associated with cancer, dementia (BRI2/ITM2b) and amyloid lung disease (proSP-C). Studies have demonstrated that it delays fibril formation and toxicity of amyloid-β peptide (Aβ) in vitro and in vivo, which plays a central role in the development of Aβ amyloid plaques, one hallmark of Alzheimer's disease (AD). It has been shown that overexpression...
Focused ultrasound (FUS) has demonstrated its ability to modulate neuronal activity in both cortical and subcortical brain regions in a noninvasive and reversible manner in mice. However, mice have very small brains relative to the size of the FUS focus. Simulations of beam profiles in rat head models have demonstrated the formation of secondary pressure peaks due to reverberations. This may explain...
Focused Ultrasound (FUS) has been shown to modulate neural activity in the brain. Our group has recently shown feasibility of FUS modulation of peripheral nerves in vivo. However, the mechanism of FUS on the peripheral nervous system (PNS) is not known and has never been imaged in vivo. In order to unveil both the mechanism as well as provide an image-guided approach to modulation monitoring, we designed...
Angiogenesis and blood flow dynamics play an important role in the development of malignant tumours and their response to treatment. While contrast enhanced ultrasound (CEUS) imaging with microbubble contrast agents as a tool for imaging angiogenesis and flow dynamics has shown great potential [1], recent development of plane wave high frame-rate (HFR) CEUS has offered new opportunities in such applications...
Plane-wave imaging has been demonstrated in humans for cardiovascular (CV) studies, but its use in mouse embryo models has received minimal attention even though the mouse is the most common experimental organism to study gene function and human disease, including CV disease (CVD). While high-frequency ultrasound Doppler modes have been used to study mouse embryo models, traditional linear-array imaging...
Focused ultrasound has been shown to interact with Alzheimer's pathology and particularly to trigger the reduction of the amyloid plaque load. However, a less studied interaction is that of ultrasound with the tangle formation that has been implicated in the cognitive decline of Alzheimer's patients. With the current study we investigate the interaction of unilateral focused ultrasound-induced blood-brain...
Thermal ablation provides local control of cancer; however, pairing ablation with immunotherapy is attractive as there is emerging evidence that focal therapy enhances the efficacy of immunotherapy. The goals of local treatment are to rapidly debulk the tumor and release tumor antigen to stimulate immune recognition. We seek to evaluate combination protocols and their tumor suppressive effects.
Focused ultrasound (FUS) with circulating microbubbles creates transient and reversible permeabilization of vasculatures which provides an essential means to deliver therapeutics and imaging agents, for instance across the BBB. We have previously shown that 3D color Doppler and photoacoustic imaging can monitor BBB disruption (BBBD) in mice. Here we study how changes in NPs size, concentration and...
Systemic chemotherapy has been associated with poor tumor penetration and adverse cytotoxic effects. To combat this, cancer therapy with in-situ forming implants (ISFIs) can provide continuous, high dose release of chemotherapeutic drug directly at the tumor site. However, poor drug distribution through the tumor volume has limited the effectiveness and subsequent translation of ISFIs into clinical...
Pancreatic cancer is an aggressive disease a 5-year-survival rate less than 7%. To improve the patient overall survival, recent developments in pancreatic cancer research have been targeting various components of the tumor microenvironment such as the extracellular matrix, blood vessels and immune cells. We hypothesize that targeted therapies will affect the biomechanics of the tumor microenvironment...
Prostate cancer biopsies are increasingly guided by ultrasound (US) imaging, yet poor soft tissue contrast makes delineation between normal/abnormal tissue difficult. There is growing interest in US contrast agents (USCA) to improve differentiation of tumors within the prostate gland and facilitate US-guided biopsies. The most widely used formulations are lipid or protein-stabilized perfluorocarbon...
Focused ultrasound and microbubbles have been shown to locally and noninvasively open the blood-brain barrier. Despite encouraging results in human patients, several performance and safety features, such as poor drug distribution, high drug accumulation along vessels and small sites of red blood cell extravasation, have been unavoidable. We have recently developed a new ultrasound sequence — rapid...
Recently, ultrafast ultrasound imaging has been proposed for many clinical applications. However, most operational frequencies of ultrafast ultrasound imaging are around 3.5 to 15 MHz. Currently, ultrafast 40 MHz high frequency ultrasound imaging has been developed in our Lab. High frequency ultrasound is a good choice for blood flow mapping because the backscattering signals from blood is increased...
Microbubbles (MBs) are capable of binding specifically to molecular markers on the vascular endothelium to enable sensitive detection of early stage disease. Traditional microbubble imaging techniques rely on the nonlinearity of microbubble signal to differentiate it from surrounding tissue. However, the presence of harmonic energy among echogenic tissue interfaces can limit the effectiveness of these...
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