Publications by authors named "Keith Stantz"

Infrared neural stimulation (INS) is an optical stimulation technique which uses coherent light to stimulate nerves and neurons and which shows increased spatial selectivity compared to electrical stimulation. This could improve deep brain, high channel count, or vagus nerve stimulation. In this study, we seek to understand the wavelength dependence of INS in the near-infrared optical window.

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Background And Purpose: Ultrasound (US) is a non-invasive, non-radiographic imaging technique with high spatial and temporal resolution that can be used for localizing soft-tissue structures and tumors in real-time during radiotherapy (RT) (inter- and intra-fraction). A comprehensive approach incorporating an in-house 3D-US system within RT is presented. This system is easier to adopt into existing treatment protocols than current US based systems, with the aim of providing millimeter intra-fraction alignment errors and sensitivity to track intra-fraction bladder movement.

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A three-dimensional photon dosimetry in tissues is critical in designing optical therapeutic protocols to trigger light-activated drug release. The objective of this study is to investigate the feasibility of a Monte Carlo-based optical therapy planning software by developing dosimetry tools to characterize and cross-validate the local photon fluence in brain tissue, as part of a long-term strategy to quantify the effects of photoactivated drug release in brain tumors. An existing GPU-based 3D Monte Carlo (MC) code was modified to simulate near-infrared photon transport with differing laser beam profiles within phantoms of skull bone (B), white matter (WM), and gray matter (GM).

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Background: Tumor hypoxia is involved in every stage of solid tumor development: formation, progression, metastasis, and apoptosis. Two types of hypoxia exist in tumors-chronic hypoxia and acute hypoxia. Recent studies indicate that the regional hypoxia kinetics is closely linked to metastasis and therapeutic responses, but regional hypoxia kinetics is hard to measure.

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Over the past decades, little progress has been made to improve the extremely low survival rates in pancreatic cancer patients. Extreme hypoxia observed in pancreatic tumors contributes to the aggressive and metastatic characteristics of this tumor and can reduce the effectiveness of conventional radiation therapy and chemotherapy. In an attempt to reduce hypoxia-induced obstacles to effective radiation treatment, we used a novel device, the implantable micro-oxygen generator (IMOG), for in situ tumor oxygenation.

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The Follicle-Stimulating Hormone Receptor (FSHR) is used as an imaging biomarker for the detection of ovarian cancer (OC). FSHR is highly expressed on ovarian tumors and involved with cancer development and metastatic signaling pathways. A decapeptide specific to the FSHR extracellular domain is synthesized and conjugated to fluorescent dyes to image OC cells and tumors xenograft model .

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Purpose: The objective of this study is to establish the feasibility of using radiation-induced acoustics to measure the range and Bragg peak dose from a pulsed proton beam. Simulation studies implementing a prototype scanner design based on computed tomographic methods were performed to investigate the sensitivity to proton range and integral dose.

Methods: Derived from thermodynamic wave equation, the pressure signals generated from the dose deposited from a pulsed proton beam with a 1 cm lateral beam width and a range of 16, 20, and 27 cm in water using Monte Carlo methods were simulated.

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Purpose: To image the intratumor vascular physiological status of pancreatic tumors xenografts and their response to anti-angiogenic therapy using dynamic contrast-enhanced computed tomography (DCE-CT), and to identify parameters of vascular physiology associated with tumor x-ray sensitivity after anti-angiogenic therapy.

Methods And Materials: Nude mice bearing human BxPC-3 pancreatic tumor xenografts were treated with 5 Gy of radiation therapy (RT), either a low dose (40 mg/kg) or a high dose (150 mg/kg) of DC101, the anti-VEGF receptor-2 anti-angiogenesis antibody, or with combination of low or high dose DC101 and 5 Gy RT (DC101-plus-RT). DCE-CT scans were longitudinally acquired over a 3-week period post-DC101 treatment.

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Background: Pancreatic cancer remains one of the deadliest cancers due to lack of early detection and absence of effective treatments. Gemcitabine, the current standard-of-care chemotherapy for pancreatic cancer, has limited clinical benefit. Treatment of pancreatic cancer cells with gemcitabine has been shown to induce the activity of the transcription factor nuclear factor-kappaB (NF-κB) which regulates the expression of genes involved in the inflammatory response and tumorigenesis.

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As systemic cancer therapies improve and are able to control metastatic disease outside the central nervous system, the brain is increasingly the first site of relapse. The blood-brain barrier (BBB) represents a major challenge to the delivery of therapeutics to the brain. Macrophages originating from circulating monocytes are able to infiltrate brain metastases while the BBB is intact.

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Purpose: The purpose of this study was to quantify and model the longitudinal intra-tumor physiological response to a single dose of a monoclonal antibody specific to the VEGFR2 using dynamic contrast-enhanced CT.

Material And Methods: Dynamic contrast-enhanced CT imaging was performed on athymic nude mice bearing xenograft VEGF-transfected MCF-7 tumors (MCF7(VEGF)) to quantify intra-tumor physiology pre- and post-injection (days 2, 7, and 14) of a nonspecific (IgG1, controls) and specific (DC101, treated) monoclonal antibody targeting VEGFR2. Parametrical maps of tumor physiology-perfusion (F), permeability surface area (PS), fractional plasma (f(p)), and interstitial space (f (is))-were obtained at four time points over a 2-week period.

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The objective of this study is to evaluate the ability of dynamic contrast enhanced computed tomography (DCE-CT) to assess intratumor physiological heterogeneity in tumors with different angiogenic phenotypes. DCE-CT imaging was performed on athymic nude mice bearing xenograft wild type (MCF-7(neo)) and VEGF-transfected (MCF-7(VEGF)) tumors by using a clinical multislice CT, and compared to skeletal muscle. Parametrical maps of tumor physiology--perfusion (F), permeability-surface area (PS), fractional intravascular plasma (f(p)), and interstitial space (f(is))--were obtained by fitting the time-dependent contrast-enhanced curves to a two-compartmental kinetic model for each voxel (0.

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In vivo bioluminescence imaging is becoming a very important tool for the study of a variety of cellular and molecular events or disease processes in living systems. In vivo bioluminescence imaging is based on the detection of light emitted from within an animal. The light is generated as a product of the luciferase-luciferin reaction taking place in a cell.

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The purpose of this study is to measure the progressive intra-tumor heterogeneous physiological states for prostate (CWRrv) and ovarian (SKOV3x) xenograft mouse models. Dynamic contrast-enhanced CT was used to measure the change in a tumor's physiological state when transitioning from stage I (<7 mm diameter) to stage II (7-20 mm diameter). Images from stage I tumors are in the initial stages of angiogenesis: neovasculature growth.

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New carbon-11 labeled D-luciferin analogs D-luciferin [(11)C]methyl ester ([(11)C]LMEster, [(11)C]1) and D-luciferin [(11)C]methyl ether ([(11)C]LMEther, [(11)C]2) were synthesized in 25-55% radiochemical yield. PET studies with [(11)C]LMEster and [(11)C]LMEther demonstrate a lower retention of the C-11 label at 45 min post-injection in luciferase expression tumor. Optical imaging with unlabeled substrate D-luciferin and radiotracers [(11)C]LMEster and [(11)C]LMEther gave tumor luciferase images within a few minutes of photon counting.

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X-ray computed tomography (CT) has been traditionally used for morphologic analysis and in the recent past has been used for physiology imaging. This paper seeks to demonstrate functional CT as an effective tool for monitoring changes in tissue physiology associated with disease processes and cellular and molecular level therapeutic processes. We investigated the effect of noise and sampling time on the uncertainty of tissue physiologic parameters.

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PSES is a chimeric enhancer containing enhancer elements from prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) genes that are prevalently expressed in androgen-independent prostate cancers. PSES shows strong activity equivalent to cytomegalovirus (CMV) promoter, specifically in PSA/PSMA-positive prostate cancer cells, the major cell types in prostate cancer in the absence of androgen. We developed a recombinant adenovirus (AdE4PSESE1a) by placing adenoviral E1a and E4 genes under the control of the bidirectional enhancer PSES and enhanced green fluorescent protein gene for the purpose of intratumoral virus tracking under the control of CMV promoter.

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