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

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

Characterizing Short-Wave Infrared Fluorescence of Conventional Near-Infrared Fluorophores

The observed behavior of short-wave infrared (SWIR) light in tissue, characterized by relatively low scatter and subdiffuse photon transport, has generated considerable interest for the potential of SWIR imaging to produce high-resolution, subsurface images of fluorescence activity in vivo. These properties have important implications for fluorescence-guided surgery and preclinical biomedical research. Until recently, translational efforts have been impeded by the conventional understanding that fluorescence molecular imaging in the SWIR regime requires custom molecular probes that do not yet have proven safety profiles in humans. However, recent studies have shown that two readily available near-infrared (NIR-I) fluorophores produce measurable SWIR fluorescence, implying that other conventional fluorophores produce detectable fluorescence in the SWIR window. Using SWIR spectroscopy and wide-field SWIR imaging with tissue-simulating phantoms, we characterize and compare the SWIR emission properties of eight commercially available red/NIR-I fluorophores commonly used in preclinical and clinical research, in addition to a SWIR-specific fluorophore. All fluorophores produce measurable fluorescence emission in the SWIR, including shorter wavelength dyes such as Alexa Fluor 633 and methylene blue. This study is the first to report SWIR fluorescence from six of the eight conventional fluorophores and establishes an important comparative reference for developing and evaluating SWIR imaging strategies for biomedical applications

Cherenkov Excited Short-Wavelength Infrared Fluorescence Imaging in vivo with External Beam Radiation

Cherenkov emission induced by external beam radiation therapy from a clinical linear accelerator (LINAC) can be used to excite phosphors deep in biological tissues. As with all luminescence imaging, there is a desire to minimize the spectral overlap between the excitation light and emission wavelengths, here between the Cherenkov and the phosphor. Cherenkov excited short-wavelength infrared (SWIR, 1000 to 1700 nm) fluorescence imaging has been demonstrated for the first time, using long Stokes-shift fluorophore PdSe quantum dots (QD) with nanosecond lifetime and an optimized SWIR detection. The 1  /  λ2 intensity spectrum characteristic of Cherenkov emission leads to low overlap of this into the fluorescence spectrum of PdSe QDs in the SWIR range. Additionally, using a SWIR camera itself inherently ignores the stronger Cherenkov emission wavelengths dominant across the visible spectrum. The SWIR luminescence was shown to extend the depth sensitivity of Cherenkov imaging, which could be used for applications in radiotherapy sensing and imaging in human tissue with targeted molecular probes

Radiotherapy-Induced Cherenkov Luminescence Imaging in a Human Body Phantom

Radiation therapy produces Cherenkov optical emission in tissue, and this light can be utilized to activate molecular probes. The feasibility of sensing luminescence from a tissue molecular oxygen sensor from within a human body phantom was examined using the geometry of the axillary lymph node region. Detection of regions down to 30-mm deep was feasible with submillimeter spatial resolution with the total quantity of the phosphorescent sensor PtG4 near 1 nanomole. Radiation sheet scanning in an epi-illumination geometry provided optimal coverage, and maximum intensity projection images provided illustration of the concept. This work provides the preliminary information needed to attempt this type of imaging in vivo

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

Intergenerational impacts of maternal mortality: Qualitative findings from rural Malawi

Background: Maternal mortality, although largely preventable, remains unacceptably high in developing countries such as Malawi and creates a number of intergenerational impacts. Few studies have investigated the far-reaching impacts of maternal death beyond infant survival. This study demonstrates the short- and long-term impacts of maternal death on children, families, and the community in order to raise awareness of the true costs of maternal mortality and poor maternal health care in Neno, a rural and remote district in Malawi. Methods: Qualitative in-depth interviews were conducted to assess the impact of maternal mortality on child, family, and community well-being. We conducted 20 key informant interviews, 20 stakeholder interviews, and six sex-stratified focus group discussions in the seven health centers that cover the district. Transcripts were translated, coded, and analyzed in NVivo 10. Results: Participants noted a number of far-reaching impacts on orphaned children, their new caretakers, and extended families following a maternal death. Female relatives typically took on caregiving responsibilities for orphaned children, regardless of the accompanying financial hardship and frequent lack of familial or governmental support. Maternal death exacerbated children’s vulnerabilities to long-term health and social impacts related to nutrition, education, employment, early partnership, pregnancy, and caretaking. Impacts were particularly salient for female children who were often forced to take on the majority of the household responsibilities. Participants cited a number of barriers to accessing quality child health care or support services, and many were unaware of programming available to assist them in raising orphaned children or how to access these services. Conclusions: In order to both reduce preventable maternal mortality and diminish the impacts on children, extended families, and communities, our findings highlight the importance of financing and implementing universal access to emergency obstetric and neonatal care, and contraception, as well as social protection programs, including among remote populations

Cherenkov-excited luminescence sheet imaging (CELSI) tomographic reconstruction

A tomographic reconstruction algorithm for Cherenkov-excited luminescence scanned imaging (CELSI) is proposed and demonstrated for the first time, to reconstruct distributions of luminescent source. Coupled continuous wave (CW) diffusion equations are used to model luminescent photon propagation in biological tissues. The CELSI reconstruction was achieved by minimizing the difference between measured and computed data based on Tikhonov regularization technique. The feasibility and effectiveness of the algorithm were tested with numerical simulations on noisy data. In addition, comparisons between conventional diffuse optical fluorescence tomography (DOFT) and CELSI were also performed. Contrast-detail analysis was also used to evaluate the imaging performance of CELSI.</p

Highest resolution whole body molecular imaging: Cherenkov excited luminescence scanned imaging

Whole body animal cherenkov excited luminescence sheet imaging (CELSI) was demonstrated in tissue phantoms as well as with a tumor bearing mouse to illustrate how the technique recovers high resolution through inhomogeneous tissue[1, 2]. Briefly, the beam from a standard radiation therapy linear accelerator is used as a thin sheet, as shaped by the multileaf collimators, 5mm thick and up to 60cm wide. The beam is swept up and down aross the tissue to be imaged in 0.1mm steps, achieving high precision localization of the excitation source in the tissue. The radiation sheet excites Cherenkov light throughout the tissue volume, and this light is the excitation source for molecular probes in the tissue. In this case, the oxygen senstitive probe, PtG4, a dendritic palladium porphyrin was used which has a phosphorescence lifetime sensitive to the pO2 value[3]. The set up is shown in Fig 1, along with raw data in (b), mapping of the surface data into a 2D image results in (c), with Max Intensity Projection (MIP) image, reconstruction of the data leads to the images in (d) and (e). Cherenkov targeted excitation of photosensitizer agents is also possible as has been shown recently, and using agents that take advantage of the high UV light yield, and intimate phototransfer to sensitizers or produce radical speicies effeciently. The comparative yields of scintillating particles relative to Cherenkov mediated excitation will be show, based upon Monte Carlo results and light fluence estimates. Please click Additional Files below to see the full abstract