Fluence rate-dependent kinetics of light-triggered liposomal doxorubicin assessed by quantitative fluorescence-based endoscopic probe.

Liposomal doxorubicin (Dox), a treatment option for recurrent ovarian cancer, often suffers from suboptimal biodistribution and efficacy, which might be addressed with precision drug delivery systems. Here, we introduce a catheter-based endoscopic probe designed for multispectral, quantitative monitoring of light-triggered drug release. This tool utilizes red-light photosensitive porphyrin-phospholipid (PoP), which is encapsulated in liposome bilayers to enhance targeted drug delivery.

Fluence rate-dependent kinetics of light-triggered liposomal doxorubicin assessed by quantitative fluorescence-based endoscopic probe.

Liposomal doxorubicin (Dox), a treatment option for recurrent ovarian cancer, often suffers from suboptimal biodistribution and efficacy, which might be addressed with precision drug delivery systems. Here, we introduce a catheter-based endoscopic probe designed for multispectral, quantitative monitoring of light-triggered drug release. This tool utilizes red-light photosensitive porphyrin-phospholipid (PoP), which is encapsulated in liposome bilayers to enhance targeted drug delivery.

A Preliminary Study of Quantitative Ultrasound for Cancer-Risk Assessment of Thyroid Nodules.

Background: Gray-scale, B-mode ultrasound (US) imaging is part of the standard clinical procedure for evaluating thyroid nodules (TNs). It is limited by its instrument- and operator-dependence and inter-observer variability. In addition, the accepted high-risk B-mode US TN features are more specific for detecting classic papillary thyroid cancer rather than the follicular variant of papillary thyroid cancer or follicular thyroid cancer.

High-frame-rate volume imaging using sparse-random-aperture compounding.

High-frame-rate volume imaging (HFR-VI) aims to provide high-quality images with high-temporal information. Despite its potential, HFR-VI translation into clinical applications has been challenging due to the high cost of the equipment required to drive matrix probes with a large number of elements. The goal of this study is to introduce and test sparse-random-aperture compounding (SRAC), a technique that allows use of matrix probes with an ultrasound system that has fewer channels while maintaining high frame rates.

Quantifying skin photodamage with spatial frequency domain imaging: statistical results.

We investigated the change in optical properties and vascular parameters to characterize skin tissue from mild photodamage to actinic keratosis (AK) with comparison to a published photodamage scale. Multi-wavelength spatial frequency domain imaging (SFDI) measurements were performed on the dorsal forearms of 55 adult subjects with various amounts of photodamage. Dermatologists rated the levels of photodamage based upon the photographs in blinded fashion to allow comparison with SFDI data.

Regional changes in the elastic properties of myopic Guinea pig sclera.

Biomechanical changes in the sclera likely underlie the excessive eye elongation of axial myopia. We studied the biomechanical characteristics of myopic sclera at the microscopic level using scanning acoustic microscopy (SAM) with 7-μm in-plane resolution. Guinea pigs underwent form-deprivation (FD) in one eye from 4 to 12 days of age to induce myopia, and 12-μm-thick scleral cryosections were scanned using a custom-made SAM.

Cerebellar folding is initiated by mechanical constraints on a fluid-like layer without a cellular pre-pattern.

Models based in differential expansion of elastic material, axonal constraints, directed growth, or multi-phasic combinations have been proposed to explain brain folding. However, the cellular and physical processes present during folding have not been defined. We used the murine cerebellum to challenge folding models with in vivo data.

Autoregressive Signal Processing Applied to High-Frequency Acoustic Microscopy of Soft Tissues.

Quantitative acoustic microscopy (QAM) at frequencies exceeding 100 MHz has become an established imaging tool to depict acoustical and mechanical properties of soft biological tissues at microscopic resolutions. In this study, we investigate a novel autoregressive (AR) model to improve signal processing and parameter estimation and to test its applicability to QAM. The performance of the AR model for estimating acoustical parameters of soft tissues (i.

Early assessment of burn severity in human tissue ex vivo with multi-wavelength spatial frequency domain imaging.

Early knowledge about burn severity and depth can lead to improved outcome for patients. In this study, we investigated the change in optical properties in ex vivo human skin following thermal burn injuries. Human skin removed during body contouring procedures was subjected to thermal burn injury for either 10 or 60 s.

Improved High-Frequency Ultrasound Corneal Biometric Accuracy by Micrometer-Resolution Acoustic-Property Maps of the Cornea.

Purpose: Mapping of epithelial thickness (ET) is useful for detection of keratoconus, a disease characterized by corneal thinning and bulging in which epithelial thinning occurs over the apex. In prior clinical studies, optical coherence tomography (OCT) measurements of ET were systematically thinner than those obtained by 40-MHz high-frequency ultrasound (HFU) where a constant speed of sound () of 1636 m/s was used for all corneal layers. The purpose of this work was to study the acoustic properties, that is, , acoustic impedance (), and attenuation () of the corneal epithelium and stroma independently using a scanning acoustic microscope (SAM) to investigate the discrepancy between OCT and HFU estimates of ET.

High-Frequency Quantitative Ultrasound for Imaging Prostate Cancer Using a Novel Micro-Ultrasound Scanner.

Currently, biopsies guided by transrectal ultrasound (TRUS) are the only method for definitive diagnosis of prostate cancer. Studies by our group suggest that quantitative ultrasound (QUS) could provide a more sensitive means of targeting biopsies and directing focal treatments to cancer-suspicious regions in the prostate. Previous studies have utilized ultrasound signals at typical clinical frequencies, i.

A dual-channel endoscope for quantitative imaging, monitoring, and triggering of doxorubicin release from liposomes in living mice.

Doxorubicin (Dox) is approved for use in liposomal form for the treatment of ovarian cancer. We previously developed a long-circulating Dox formulation in liposomes containing small amounts of porphyrin-phospholipid, which enables on-demand drug release with near-infrared irradiation. In this study, we present and evaluate a dual-modal, dual-channel light endoscope that allows quantitative reflectance and fluorescence imaging for monitoring of local Dox concentrations in target areas.

Resting-state functional connectivity measured by diffuse correlation spectroscopy.

Near-infrared diffuse correlation spectroscopy (DCS) is used to record spontaneous cerebral blood flow fluctuations in the frontal cortex. Nine adult subjects participated in the experiments, in which 8-minute spontaneous fluctuations were simultaneously recorded from the left and right dorsolateral and inferior frontal regions. Resting-state functional connectivity (RSFC) was measured by the temporal correlation of the low frequency fluctuations.

Material Properties of Human Ocular Tissue at 7-µm Resolution.

Quantitative assessment of the material properties of ocular tissues can provide valuable information for investigating several ophthalmic diseases. Quantitative acoustic microscopy (QAM) offers a means of obtaining such information, but few QAM investigations have been conducted on human ocular tissue. We imaged the optic nerve (ON) and iridocorneal angle in 12-µm deparaffinized sections of the human eye using a custom-built acoustic microscope with a 250-MHz transducer (7-µm lateral resolution).

Noninvasive mesoscopic imaging of actinic skin damage using spatial frequency domain imaging.

For prevention and accurate intervention planning, it is crucial to predict if lesions will progress towards cancer. In this study, we investigated the change in optical properties and vascular parameters to characterize skin tissue from mild photodamage to actinic keratosis (AK). Multi-wavelength spatial frequency domain imaging (SFDI) measurements were performed on three patients with clinically normal skin, as well as pre-cancerous actinic keratosis lesions.

Optical imaging of tissue obtained by transbronchial biopsies of peripheral lung lesions.

Background: Bronchoscopic procedures have been increasingly used for the diagnosis of peripheral lung cancers, but the yield remains moderately low. The aim of this study is to assess the feasibility and ability of a custom-built bimodal optical spectroscopy system to enhance the on-site discrimination between malignant and benign specimens obtained from the transbronchial lung biopsies (TBLB) of peripheral lung lesions.

Methods: We conducted a prospective and single-center pilot study to examine the TBLB specimens obtained from peripheral lung lesions.

Regular chondrocyte spacing is a potential cause for coherent ultrasound backscatter in human articular cartilage.

The potential of quantitative ultrasound (QUS) to assess the regular cellular spacing in the superficial cartilage zones was investigated experimentally and numerically. Nine osteochondral samples, extracted from two human cadaver knee joints, were measured using a 50-MHz ultrasound scanning device and evaluated using Mankin score. Simulated backscattered power spectra from models with an idealized cell alignment exhibited a pronounced frequency peak.

Structural and Epimeric Isomers of HPPH [3-Devinyl 3-{1-(1-hexyloxy) ethyl}pyropheophorbide-a]: Effects on Uptake and Photodynamic Therapy of Cancer.

The tetrapyrrole structure of porphyrins used as photosentizing agents is thought to determine uptake and retention by malignant epithelial cancer cells. To assess the contribution of the oxidized state of individual rings to these cellular processes, bacteriochlorophyll a was converted into the ring "D" reduced 3-devinyl-3-[1-(1-hexyloxy)ethyl]pyropheophorbide-a (HPPH) and the corresponding ring "B" reduced isomer (iso-HPPH). The carboxylic acid analogs of both ring "B" and ring "D" reduced isomers showed several-fold higher accumulation into the mitochondria and endoplasmic reticulum by primary culture of human lung and head and neck cancer cells than the corresponding methyl ester analogs that localize primarily to granular vesicles and to a lesser extent to mitochondria.

A Novel Quantitative 500-MHz Acoustic Microscopy System for Ophthalmologic Tissues.

Objective: This paper describes development of a novel 500-MHz scanning acoustic microscope (SAM) for assessing the mechanical properties of ocular tissues at fine resolution. The mechanical properties of some ocular tissues, such as lamina cribrosa (LC) in the optic nerve head, are believed to play a pivotal role in eye pathogenesis.

Methods: A novel etching technology was used to fabricate silicon-based lens for a 500-MHz transducer.

Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma.

This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR).

Quantitative imaging of light-triggered doxorubicin release.

The efficacy of chemotherapy is related, in large part, to the concentration of drug that reaches tumor sites. Doxorubicin (DOX) is a common anti-cancer drug that is also approved for use in liposomal form for the treatment of ovarian cancer. We recently developed a porphyrin-phospholipid (PoP)-liposome system that enables on demand release of DOX from liposomes using near infrared irradiation to improve DOX bioavailability.

Characterization of nonmelanoma skin cancer for light therapy using spatial frequency domain imaging.

The dosimetry of light-based therapies critically depends on both optical and vascular parameters. We utilized spatial frequency domain imaging to quantify optical and vascular parameters, as well as estimated light penetration depth from 17 nonmelanoma skin cancer patients. Our data indicates that there exist substantial spatial variations in these parameters.

Fine-resolution maps of acoustic properties at 250 MHz of unstained fixed murine retinal layers.

Ex vivo assessment of microscale tissue biomechanical properties of the mammalian retina could offer insights into diseases such as keratoconus, and macular degeneration. A 250-MHz scanning acoustic microscope (7-μm resolution) has been constructed to derive two-dimensional quantitative maps of attenuation (α), speed of sound (c), acoustic impedance (Z), bulk modulus (B), and mass density ( ρ). The two-dimensional maps were compared to coregistered hematoxylin-and-eosin stained sections.

Distribution of mesoscale elastic properties and mass density in the human femoral shaft.

Cortical bone properties are determined by tissue composition and structure at several hierarchical length scales. In this study, the spatial distribution of micro- and mesoscale elastic properties within a human femoral shaft has been investigated. Microscale tissue degree of mineralization (DMB), cortical vascular porosity Ct.