Chris Bonnerup

Absolute calibration of optical power for PDT: Report of AAPM TG140

This report is primarily concerned with methods for optical calibration of laser power for continuous wave (CW) light sources, predominantly used in photodynamic therapy (PDT). Light power calibration is very important for PDT, however, no clear standard has been established for the calibration procedure nor the requirements of power meters suitable for optical power calibration. The purposes of the report are to provide guidance for establishing calibration procedures for thermopile type power meters and establish calibration uncertainties for most commercially available detectors and readout assemblies. The authors have also provided a review of the use of various power meters for CW and pulsed optical sources, and provided recommended temporal frequencies for optical power meter calibrations and guidance for routine quality assurance procedure.

RT-qPCR for Fecal Mature MicroRNA Quantification and Validation

By routinely and systematically being able to perform quantitative stem-loop reverse transcriptase (RT) followed by TaqMan® minor-groove binding (MGB) probe, real-time quantitative PCR analysis on exfoliated enriched colonocytes in stool, using human (Homo sapiens, hsa) micro(mi)RNAs to monitor changes of their expression at various stages of colorectal (CRC) progression, this method allows for the reliable and quantitative diagnostic screening of colon cancer (CC). Although the expression of some miRNA genes tested in tissue shows less variability in normal or cancerous patients than in stool, the noninvasive stool by itself is well suited for CC screening. An miRNA approach using stool promises to offer more sensitivity and specificity than currently used genomic, methylomic, or proteomic methods for CC screening.To present an application of employing miRNAs as diagnostic markers for CC screening, we carried out global microarray expression studies on stool colonocytes isolated by paramagnetic beads, using Affymetrix GeneChip miRNA 3.0 Array, to select a panel of miRNAs for subsequent focused semiquantitative PCR analysis studies. We then conducted a stem-loop RT-TaqMan® MGB probes, followed by a modified real-time qPCR expression study on 20 selected miRNAs for subsequent validation of the extracted immunocaptured total small RNA isolated from stool colonocytes. Results showed 12 miRNAs (miR-7, miR-17, miR-20a, miR-21, miR-92a, miR-96, miR-106a, miR-134, miR-183, miR-196a, miR-199a-3p, and miR214) to have an increased expression in stool of CC patients, and that later TNM stages exhibited more increased expressions than adenomas, while 8 miRNAs (miR-9, miR-29b, miR-127-5p, miR-138, miR-143, miR-146a, miR-222, and miR-938) showed decreased expressions in stool of CC patients, which becomes more pronounced as the cancer progresses from early to late TNM stages (0-IV).

Use of MicroRNAs to Screen for Colon Cancer

Colon cancer (CC) screening is important for diagnosing early stage for malignancy and therefore potentially reduces mortality from this disease because the cancer could be cured at the early disease stage. Early detection is needed if accurate and cost effective diagnostic methods are available. Mortality from colon cancer malignancy is theoretically preventable through screening. The Current screening method, the immunological fecal occult blood test, FOBTi, lacks sensitivity and requires dietary restriction, which impedes compliance. Moreover colonoscopy is invasive and costly, which decreases compliance, and in certain cases could lead to mortality. Compared to the FOBT test, a noninvasive sensitive screen that does not require dietary restriction would be more convenient. Colonoscopy screening is recommended for colorectal cancer (CRC). Although it is a reliable screening method, colonoscopy is an invasive test, often accompanied by abdominal pain, has potential complications and has high cost, which has hampered its application worldwide. A screening approach that uses the relatively stable and non degradable micro RNA molecules when extracted from either the noninvasive human stool, or the semi-invasive blood samples by available commercial kits and manipulated thereafter, would be more preferable than a transcriptomic messenger (m) RNA-, a mutation DNA-, an epigeneticor a proteomic-based test. That approach utilizes reverse transcriptase (RT), followed by a modified quantitative real-time polymerase chain reaction (qPCR). To compensate for exosomal miRNAs that would not be measured, a parallel test could be performed on stool or plasmas total RNAs, and corrections for exsosomal loss are made to obtain accurate results. Ultimately, a chip would be developed to facilitate diagnosis, as has been carried out for the quantification of genetically modified organisms (GMOs) in foods. The gold standard to which the miRNA test is compared to is colonoscopy. If laboratory performance criteria are met, a miRNA test in human stool or blood samples based on high through put automated technologies and quantitative expression measurements currently employed in the diagnostic clinical laboratory, would eventually be advanced to the clinical setting, making a noticeable impact on the prevention of colon cancer.

WE-E-304A-04: Local Determination of Tissue Optical Properties: Reconstruction Based On Fiber-Array Reflectance Profiles

Quantitative evaluation of in vivo local tissue optical properties including scattering coefficient (μs), absorption coefficient (μa) and anisotropy (g) is often important in both photodiagnosis and phototherapy. In this study, a reflectance based fast technique was developed to determine the optical properties of turbid media using a linear‐array fiber bundle probe. Five 200 um collection fibers were linearly set along from the 200 um illumination fiber with center‐to‐center separation of 350 um. Spatial reflectance values were sequentially measured by spectrometer connected to a fiber‐switch. A model that relates the reflectance profiles to optical properties of a turbid medium was developed based on Monte Carlo simulations and phantom experiments. Simulation results at wavelength of 633 nm showed that μs′ (2∼40 cm−1) and μa (0∼5 cm−1) can be determined by reflectance spatial profiles. Intralipid and Nigrosin were used to simulate different reduced scattering coefficient (μs′) and absorption coefficient (μa) values within the same range as Monte Carlo simulation. Preliminary results show good correlation between known optical properties in tissue phantom and the measuredoptical properties, the average error for μs′ and μa was 7.8% and 6.6%, respectively. With same reduced scattering coefficient (μs′), changes in the absorption coefficient (μa) could be measured within 0.1 cm−1. Accurate extraction of tissue optical properties from in vivomeasurements could have potential application in noninvasively superficial (pre)cancer detection and phototherapy planning.

SU‐FF‐J‐19: Prototype Fixture for IGRT Coordinate Registration and 4D CT Reconstruction

Purpose: The potential use of in‐room CT technology for target localization requires accurate methods for mapping spatial and temporal data between the CT and linac coordinate spaces. This can be done by absolute calibration of the imaging device prior to scanning or by capturing known fiducial patterns within the image data. We have designed a hybrid technique for in‐room CTs that defines a unified coordinate system referenced to the treatment table. It is based on patterns encoded in the unused portion of CTimages below the treatment table surface. These patterns have two primary functions: 1) to facilitate the registration of image coordinates for image‐guided radiation therapy; and 2) to encode an external respiratory signal for 4D CTreconstruction. Methods and Materials: A fixture was made from a 6 mm thick acrylic plate embedded with small aluminum rods. The rods formed a pattern used for spatial calibration. In addition, a long “V” shaped piece of extruded aluminum was mounted on the fixture between bearings and attached to a motor. The motor was computer controlled such that the “V” could point in any direction to encode a respiratory signal. The entire fixture was mounted beneath the “tennis racket” portion of a carbon fiber treatment table. Results:CTimages clearly showed the spatial patterns and respiratory signal encoded by the fixture. Dynamic respiratory signals were imaged with minimal artifacts at angular velocities up to six rpm with 0.8s CT gantry rotation. Custom software was able to decode the image metadata and use it for IGRT coordinate registration and 4D CTreconstruction. Attenuation of 6 MV radiation by the fixture was measured to be < 3%. Conclusions: The prototype met all design goals and facilitated IGRT coordinate registration and 4D CTreconstruction.Conflict of Interest: Research sponsored by Siemens corporation.

SU-FF-T-87: Attenuation Due to Bronchial Stents in 192Ir HDR Brachytherapy

Purpose: Evaluate the radiation attenuation from bronchial stents during endobronchial 192 Ir HDR brachytherapy.Materials and Methods: The radiation attenuation of several commercially available bronchial stents was analyzed with an ionization chamber. The stents were divided into three groups: Nitinol mesh (0.5 mm thickness), polyester mesh with silicone coating (1.0 mm thickness); and solid silicone (1.5 mm thickness). A solid cerrobend cube with 9 cm sides was molded into an irradiation cell to produce a collimated beam. The cube had a 4 mm diameter hollow cylindrical shaft in its center for inserting the HDR catheter. A pyramidal shaped opening perpendicular to the axis of the cylindrical shaft served as primary collimator with 1.5 × 1.5 cm aperture. A secondary collimator with 3 × 3 cm aperture was positioned 12 cm from the source. The distance from the source to the center of the ionization chamber was 20 cm. The field size at the chamber position was 5 × 5 cm. The stents were cut longitudinally so that each could be mounted flat on the secondary collimator. The field size at the SDD was verified with Gafchromic film. The attenuation of the radiation beam was evaluated by taking the ratio between the air kerma rate at the SDD with and without the stent. Results: The Nitinol stent attenuated the beam by 0.8%, the polyester/silicone by 2.8%, and the silicone 3.3%. Conclusions: The attenuation due to bronchial stents has been measured and can be accounted for since it can be as high as 3.3%. Whether this correction is clinically relevant should be evaluated. Moreover the stent thickness can serves as spacer to help reduce the dose on the bronchial surface for as much as 20%, as determined by Monte Carlo calculation in previous publication.

SU‐FF‐T‐206: Laser Rangefinder for Automatic SSD Measurement and Inter‐Fraction Patient Movement Monitoring

Purpose:Source to Skin Surface Distance (SSD) is one of the most frequently used reference parameters for patient setup to verify the depth of treatment for external beam treatments in clinical radiotherapy. Modern machines use an Optical Distance Indicator (ODI) mounted inside the linear accelerator or a Front Pointer (FP) where the use of the ODI is precluded. In IMRT and IGRT, more precise tools are needed to monitor and record SSD, and provide information on patient movements during therapy. Additionally, automatic capture and recording of SSD data is preferential in busy clinical settings. We describe the use of a commercially available laser rangefinder to report SSD and inter‐fraction patient movement in real‐time. Method and Materials: The Acuity Research Model AR4000‐LV was evaluated as a tool to measure SSD and inter‐fraction movement. The device emits a visible laser spot (670 nm), and a time‐of‐flight measurement is obtained from the reflected beam from diffuse reflectance surfaces. Output data is provided either as a voltage or as a digital stream. The device was tested both on an optical bench (for absolute measurements) and on a phantom on the treatment couch. Tests were performed statically and during measured oscillations of the phantom. Results: Un‐calibrated accuracy was as described by the manufacturer; ±3.8 mm. However, precision was much better at ± 0.254 mm. Calibrated measurements improved accuracy to ± 1mm. Measurements on non‐planar and tilted surfaces were also tested, and were unchanged at angles up to 45°. Conclusion: We show the ability of off‐the‐shelf technology to improve the efficiency and repeatability of SSD measurements. Also, minor patient movement can be monitored in real‐time. We find the laser rangefinder to be precise, time efficient and very accurate for determining and verifying SSD. We will evaluate its use in clinical studies.