Quantitative Cherenkov emission spectroscopy for tissue oxygenation assessment

Measurements of Cherenkov emission in tissue during radiation therapy are shown to enable estimation of hemoglobin oxygen saturation non-invasively, through spectral fitting of the spontaneous emissions from the treated tissue. Tissue oxygenation plays a critical role in the efficacy of radiation therapy to kill tumor tissue. Yet in-vivo measurement of this has remained elusive in routine use because of the complexity of oxygen measurement techniques. There is a spectrally broad emission of Cherenkov light that is induced during the time of irradiation, and as this travels through tissue from the point of the radiation deposition, the tissue absorption and scatter impart spectral changes. These changes can be quantified by diffuse spectral fitting of the signal. Thus Cherenkov emission spectroscopy is demonstrated for the first time quantitatively in vitro and qualitatively in vivo, and has potential for real-time online tracking of tissue oxygen during radiation therapy when fully characterized and developed. (C) 2012 Optical Society of Americ

Multi-Beam Scan Analysis with a Clinical LINAC for High Resolution Cherenkov-Excited Molecular Luminescence Imaging in Tissue.

Cherenkov-excited luminescence scanned imaging (CELSI) is achieved with external beam radiotherapy to map out molecular luminescence intensity or lifetime in tissue. Just as in fluorescence microscopy, the choice of excitation geometry can affect the imaging time, spatial resolution and contrast recovered. In this study, the use of spatially patterned illumination was systematically studied comparing scan shapes, starting with line scan and block patterns and increasing from single beams to multiple parallel beams and then to clinically used treatment plans for radiation therapy. The image recovery was improved by a spatial-temporal modulation-demodulation method, which used the ability to capture simultaneous images of the excitation Cherenkov beam shape to deconvolve the CELSI images. Experimental studies used the multi-leaf collimator on a clinical linear accelerator (LINAC) to create the scanning patterns, and image resolution and contrast recovery were tested at different depths of tissue phantom material. As hypothesized, the smallest illumination squares achieved optimal resolution, but at the cost of lower signal and slower imaging time. Having larger excitation blocks provided superior signal but at the cost of increased radiation dose and lower resolution. Increasing the scan beams to multiple block patterns improved the performance in terms of image fidelity, lower radiation dose and faster acquisition. The spatial resolution was mostly dependent upon pixel area with an optimized side length near 38mm and a beam scan pitch of P = 0.33, and the achievable imaging depth was increased from 14mm to 18mm with sufficient resolving power for 1mm sized test objects. As a proof-of-concept, in-vivo tumor mouse imaging was performed to show 3D rendering and quantification of tissue pO2 with values of 5.6mmHg in a tumor and 77mmHg in normal tissue

Color Cherenkov imaging of clinical radiation therapy

Color vision is used throughout medicine to interpret the health and status of tissue. Ionizing radiation used in radiation therapy produces broadband white light inside tissue through the Cherenkov effect, and this light is attenuated by tissue features as it leaves the body. In this study, a novel time-gated three-channel camera was developed for the first time and was used to image color Cherenkov emission coming from patients during treatment. The spectral content was interpreted by comparison with imaging calibrated tissue phantoms. Color shades of Cherenkov emission in radiotherapy can be used to interpret tissue blood volume, oxygen saturation and major vessels within the body

Optical emission-based phantom to verify coincidence of radiotherapy and imaging isocenters on an MR-linac

PURPOSE: Demonstrate a novel phantom design using a remote camera imaging method capable of concurrently measuring the position of the x-ray isocenter and the magnetic resonance imaging (MRI) isocenter on an MR-linac. METHODS: A conical frustum with distinct geometric features was machined out of plastic. The phantom was submerged in a small water tank, and aligned using room lasers on a MRIdian MR-linac (ViewRay Inc., Cleveland, OH). The phantom physical isocenter was visualized in the MR images and related to the DICOM coordinate isocenter. To view the x-ray isocenter, an intensified CMOS camera system (DoseOptics LLC., Hanover, NH) was placed at the foot of the treatment couch, and centered such that the optical axis of the camera was coincident with the central axis of the treatment bore. Two or four 8.3mm x 24.1cm beams irradiated the phantom from cardinal directions, producing an optical ring on the conical surface of the phantom. The diameter of the ring, measured at the peak intensity, was compared to the known diameter at the position of irradiation to determine the Z-direction offset of the beam. A star-shot method was employed on the front face of the frustum to determine X-Y alignment of the MV beam. Known shifts were applied to the phantom to establish the sensitivity of the method. RESULTS: Couch translations, demonstrative of possible isocenter misalignments, on the order of 1mm were detectable for both the radiotherapy and MRI isocenters. Data acquired on the MR-linac demonstrated an average error of 0.28mm(N=10, R CONCLUSIONS: The phantom was capable of measuring both the MRI and radiotherapy treatment isocenters. This method has the potential to be of use in MR-linac commissioning, and could be streamlined to be valuable in daily constancy checks of isocenter coincidence

Optimization of in vivo Cherenkov imaging dosimetry via spectral choices for ambient background lights and filtering

SIGNIFICANCE: The Cherenkov emission spectrum overlaps with that of ambient room light sources. Choice of room lighting devices dramatically affects the efficient detection of Cherenkov emission during patient treatment. AIM: To determine optimal room light sources allowing Cherenkov emission imaging in normally lit radiotherapy treatment delivery rooms. APPROACH: A variety of commercial light sources and long-pass (LP) filters were surveyed for spectral band separation from the red to near-infrared Cherenkov light emitted by tissue. Their effects on signal-to-noise ratio (SNR), Cherenkov to background signal ratio, and image artifacts were quantified by imaging irradiated tissue equivalent phantoms with an intensified time-gated CMOS camera. RESULTS: Because Cherenkov emission from tissue lies largely in the near-infrared spectrum, a controlled choice of ambient light that avoids this spectral band is ideal, along with a camera that is maximally sensitive to it. An RGB LED light source produced the best SNR out of all sources that mimic room light temperature. A 675-nm LP filter on the camera input further reduced ambient light detected (optical density \u3e 3), achieving maximal SNR for Cherenkov emission near 40. Reduction of the room light signal reduced artifacts from specular reflection on the tissue surface and also minimized spurious Cherenkov signals from non-tissue features such as bolus. CONCLUSIONS: LP filtering during image acquisition for near-infrared light in tandem with narrow band LED illuminated rooms improves image quality, trading off the loss of red wavelengths for better removal of room light in the image. This spectral filtering is also critically important to remove specular reflection in the images and allow for imaging of Cherenkov emission through clear bolus. Beyond time-gated external beam therapy systems, the spectral separation methods can be utilized for background removal for continuous treatment delivery methods including proton pencil beam scanning systems and brachytherapy

Chemical Reaction Dynamics at Surfaces

Contains reports on four research projects.National Science Foundation (Grant DMR81-19292)National Science Foundation (Grant CHE82-06422)Research CorporationCamille and Henry Dreyfus FoundationMonsant

Two-Dimensional Distribution of Volatiles in the Lunar Regolith from Space Weathering Simulations

We present simulations of space weathering effects on ice deposits in regions of permanent shadow on the Moon. These Monte Carlo simulations follow the effects of space weathering processes on the distribution of the volatiles over time. The model output constrains the coherence of volatile deposits with depth, lateral separation, and time. The results suggest that ice sheets become broken and buried with time. As impacts begin to puncture an initially coherent surficial ice sheet, small areas with a deficit of ice compared to surrounding areas are formed first. As time progresses, holes become prevalent and the anomalous regions are local enhancements of ice concentration in a volume. The 3-D distribution is also heterogeneous because the ice is buried to varying depths in different locations. Analysis of the coherence of ice on 10 cm scales predicts that putative ice sheets in anomalous radar craters are 1000 Myr old. For future in situ analysis of cold trap volatiles, a horizontal range of 10 m is sufficient to acquire surface-based measurements of heterogeneously distributed ice. These results also support previous analyses that Mercury's cold traps are young

Characterization of a Non-Contact Imaging Scintillator-Based Dosimetry System for Total Skin Electron Therapy.

Surface dosimetry is required for ensuring effective administration of total skin electron therapy (TSET); however, its use is often reduced due to the time consuming and complex nature of acquisition. A new surface dose imaging technique was characterized in this study and found to provide accurate, rapid and remote measurement of surface doses without the need for post-exposure processing. Disc-shaped plastic scintillators (1 mm thick  ×  15 mm [Formula: see text]) were chosen as optimal-sized samples and designed to attach to a flat-faced phantom for irradiation using electron beams. Scintillator dosimeter response to radiation damage, dose rate, and temperature were studied. The effect of varying scintillator diameter and thickness on light output was evaluated. Furthermore, the scintillator emission spectra and impact of dosimeter thickness on surface dose were also quantified. Since the scintillators were custom-machined, dosimeter-to-dosimeter variation was tested. Scintillator surface dose measurements were compared to those obtained by optically stimulated luminescence dosimeters (OSLD). Light output from scintillator dosimeters evaluated in this study was insensitive to radiation damage, temperature, and dose rate. Maximum wavelength of emission was found to be 422 nm. Dose reported by scintillators was linearly related to that from OSLDs. Build-up from placement of scintillators and OSLDs had a similar effect on surface dose (4.9% increase). Variation among scintillator dosimeters was found to be 0.3  ±  0.2%. Scintillator light output increased linearly with dosimeter thickness (~1.9  ×  /mm). All dosimeter diameters tested were able to accurately measure surface dose. Scintillator dosimeters can potentially improve surface dosimetry-associated workflow for TSET in the radiation oncology clinic. Since scintillator data output can be automatically recorded to a patient medical record, the chances of human error in reading out and recording surface dose are minimized

Alcohol Consumption, Left Atrial Diameter, and Atrial Fibrillation

BACKGROUND: Alcohol consumption has been associated with atrial fibrillation (AF) in several epidemiologic studies, but the underlying mechanisms remain unknown. We sought to test the hypothesis that an atrial myopathy, manifested by echocardiographic left atrial enlargement, explains the association between chronic alcohol use and AF. METHODS AND RESULTS: We evaluated the relationship between cumulative alcohol consumption and risk of incident AF in 5220 Offspring and Original Framingham Heart Study participants (mean age 56.3 years, 54% women) with echocardiographic left atrial size measurements. The incidence of AF was 8.4 per 1000 person-years, with 1088 incident AF cases occurring over a median 6.0 years (25th-75th percentiles 4.0-8.7 years) of follow-up. After multivariable adjustment for potential confounders, every additional 10 g of alcohol per day (just under 1 drink per day) was associated with a 0.16 mm (95% CI, 0.10-0.21 mm) larger left atrial dimension. Also in multivariable adjusted analysis, every 10 g per day of alcohol consumed was associated with a 5% higher risk of developing new-onset AF (hazard ratio, 1.05; 95% CI, 1.01-1.09). An estimated 24% (95% CI, 8-75) of the association between alcohol and AF risk was explained by left atrial enlargement. CONCLUSIONS: Our study of a large, community-based sample identified alcohol consumption as a predictor of left atrial enlargement and subsequent incident AF. Left atrial enlargement may be an intermediate phenotype along the causal pathway linking long-term alcohol consumption to AF