Search

Background: Use of a linear accelerator in ultra-high dose rate (UHDR) mode can provide a conduit for wider access to UHDR FLASH effects, sparing normal tissue, but care needs to be taken in the use of such systems to ensure errors are minimized. Purpose: Failure Modes and Effects Analysis (FMEA) was carried out in a team that has been involved in converting a LINAC between clinical use and UHDR experimental mode for more than one year, following the proposed methods of TG100. Methods: A team of 9 professionals with extensive experience were polled to outline the process map and workflow for analysis, and developed fault trees for potential errors, as well as failure modes that would results. The team scored the categories of severity magnitude (S), occurrence likelihood (O), and detectability potential (D) in a scale of 1 to 10, so that a risk priority number (RPN=S*O*D) could be assessed for each. Results: A total of 46 potential failure modes were identified, including 5 with RPN>100. These failure modes involved 1) patient set up, 2) gating mechanisms in delivery, and 3) detector in the beam stop mechanism. Identified methods to mitigate errors included 1) use of a checklist post conversion, 2) use of robust radiation detectors, 3) automation of QA and beam consistency checks, and 4) implementation of surface guidance during beam delivery. Conclusions: The FMEA process was considered critically important in this setting of a new use of a LINAC, and the expert team developed a higher level of confidence in the ability to safely move UHDR LINAC use towards expanded research access., 26 Pages, 6 Figures, 4 Tables

Purpose In mono-isocentric radiation therapy treatment plans designed to treat the whole breast and supraclavicular lymph nodes, the fields meet at isocenter, forming the match line. Insufficient coverage at the match line can lead to recurrence, and overlap over weeks of treatment can lead to increased risk of healthy tissue toxicity. Cherenkov imaging was used to assess the accuracy of delivery at the match line and identify potential incidents during patient treatments. Methods and materials A controlled calibration was constructed from the deconvolved Cherenkov images from the delivery of a modified patient treatment plan to an anthropomorphic phantom with introduced separation and overlap. The trend from this calibration was then used to evaluate the field match line for accuracy and inter-fraction consistency for two patients. Results The intersection point between matching field profiles was directly correlated to the distance (gap/overlap) between the fields (anthropomorphic phantom R2 = 0.994 “breath hold” and R2 = 0.990 “free breathing”). The profile intersection points from two patients’ imaging sessions yielded an average of +1.40 mm offset (overlap) and −1.32 mm offset (gap), thereby introducing roughly a 25.0% over-dose and a −23.6% under-dose (R2 = 0.994). Conclusions This study shows that field match regions can be detected and quantified by taking deconvolved Cherenkov images and using their product image to create steep intensity gradients, causing match lines to stand out. These regions can then be quantitatively translated into a dose consequence. This approach offers a high sensitivity detection method which can quantify match line variability and errors in vivo.

Background and Aims Locally advanced pancreatic cancer (LAPC) often causes obstruction. Verteporfin photodynamic therapy (PDT) can feasibly “debulk” the tumor more safely than noncurative surgery and has multiple advantages over older PDT agents. We aimed to assess the feasibility of EUS-guided verteporfin PDT in ablating nonresectable LAPC. Methods Adults with LAPC with adequate biliary drainage were prospectively enrolled. Exclusion criteria were significant metastatic disease burden, disease involving >50% duodenal or major artery circumference, and recent treatment with curative intent. CT was obtained between days –28 to 0. On day 0, verteporfin .4 mg/kg was infused 60 to 90 minutes before EUS, during which a diffuser was positioned in the tumor and delivered light at 50 J/cm for 333 seconds. CT was obtained on day 2, with adverse event monitoring occurring on days 1, 2, and 14. The primary outcome was presence of necrosis. Results Of 8 patients (62.5% men, mean age 65 ± 7.9 years) included in the study, 5 were staged at T3, 2 at T2, and 1 at T1. Most (n = 4) had primary lesions in the pancreatic head. Mean pretrial tumor diameter was 33.3 ± 13.4 mm. On day 2 CT, 5 lesions demonstrated a zone of necrosis measuring a mean diameter of 15.7 ± 5.5 mm; 3 cases did not develop necrosis. No adverse events were noted during the procedure or postprocedure observation period (days 1-3), and no changes in patient-reported outcomes were noted. Conclusions In this pilot study, EUS-guided verteporfin PDT is feasible and shows promise as a minimally invasive ablative therapy for LAPC in select patients. Tumor necrosis is visible within 48 hours after treatment. Patient enrollment and data collection are ongoing. (Clinical trial registration number: NCT03033225.)

Purpose The value of Cherenkov imaging as an on-patient, real-time, treatment delivery verification system was examined in a 64-patient cohort during routine radiation treatments in a single-center study. Methods and Materials Cherenkov cameras were mounted in treatment rooms and used to image patients during their standard radiation therapy regimen for various sites, predominantly for whole breast and total skin electron therapy. For most patients, multiple fractions were imaged, with some involving bolus or scintillators on the skin. Measures of repeatability were calculated with a mean distance to conformity (MDC) for breast irradiation images. Results In breast treatments, Cherenkov images identified fractions when treatment delivery resulted in dose on the contralateral breast, the arm, or the chin and found nonideal bolus positioning. In sarcoma treatments, safe positioning of the contralateral leg was monitored. For all 199 imaged breast treatment fields, the interfraction MDC was within 7 mm compared with the first day of treatment (with only 7.5% of treatments exceeding 3 mm), and all but 1 fell within 7 mm relative to the treatment plan. The value of imaging dose through clear bolus or quantifying surface dose with scintillator dots was examined. Cherenkov imaging also was able to assess field match lines in cerebral-spinal and breast irradiation with nodes. Treatment imaging of other anatomic sites confirmed the value of surface dose imaging more broadly. Conclusions Daily radiation therapy can be imaged routinely via Cherenkov emissions. Both the real-time images and the posttreatment, cumulative images provide surrogate maps of surface dose delivery that can be used for incident discovery and/or continuous improvement in many delivery techniques. In this initial 64-patient cohort, we discovered 6 minor incidents using Cherenkov imaging; these otherwise would have gone undetected. In addition, imaging provides automated, quantitative metrics useful for determining the quality of radiation therapy delivery.

Background Daylight-activated PDT has seen increased support in recent years as a treatment method for actinic keratosis and other non-melanoma skin cancers. The inherent variability observed in broad-spectrum light used in this methodology makes it difficult to plan and monitor light dose, or compare to lamp light doses. Methods The present study expands on the commonly used PpIX-weighted effective surface irradiance metric by introducing a Monte Carlo method for estimating effective fluence rates into depths of the skin. The fluence rates are compared between multiple broadband and narrowband sources that have been reported in previous studies, and an effective total fluence for various treatment times is reported. A dynamic estimate of PpIX concentration produced during pro-drug incubation and treatment is used with the fluence estimates to calculate a photodynamic dose. Results Even when there is up to a 5x reduction between the effective surface irradiance of the broadband light sources, the effective fluence below 250 μm depth is predicted to be relatively equivalent. An effective threshold fluence value (0. 70 J e f f / c m 2 ) is introduced based on a meta-analysis of previously published ALA-PpIX induced cell death. This was combined with a threshold PpIX concentration (50 nM) to define a threshold photodynamic dose of 0.035 u M J e f f / c m 2 . Conclusions The threshold was used to generate lookup tables to prescribe minimal treatment times to achieve depth-dependent cytotoxic effect based on incubation times and irradiance values for each light source.

Breast-conserving surgery requires that resection margins be cancer-free, but re-excision rates due to positive margins have remained near 20% for much of the last decade with high variability between surgical centers. Recent studies have demonstrated that volumetric X-ray imaging improves margin assessment over standard techniques, given the speed of image reconstruction and full three-dimensional sensing of all margins. Deep learning approaches for automated analysis of volumetric medical image data are gaining traction and could play an important role streamlining the clinical workflow for intra-surgical specimen imaging. X-ray imaging systems currently deployed in clinical studies suffer from poor tumor-to-fibroglandular tissue contrast, motivating the development of adjuvant tools that could potentially complement volumetric X-ray scanning and further improve the future of intra-surgical margin assessment by real-time augmented guidance for the surgeon.

Purpose/Objective(s) In the last decade, Cherenkov imaging has been demonstrated as a useful clinical technique both for real-time surface dose visualization during patient treatment and for various high-resolution QA measurements. However there remains much work to be done in the development of Cherenkov-based in vivo dosimetry. In this work, the concept of in vivo color Cherenkov imaging is introduced. It is hypothesized that Cherenkov images with sensitivity to the spectral quality of Cherenkov emission induced inside tissue can provide increased information about tissue composition as opposed to monochromatic, red-weighted images used in prior work. Materials/Methods A custom Color Cherenkov camera was created from three time-gated intensified CMOS cameras, each with varying spectral sensitivity of the photocathode, and sharing one imaging lens. A dichroic mirror assembly allowed for incoming Cherenkov light signals to be redirected according to wavelength to the appropriate camera resulting in three raw image stacks for each acquisition. These images were then reconstructed into three-channel color images via color calibration, summed, and background subtracted. In vivo color Cherenkov images of three right-sided breast patients were acquired for one treatment fraction each as part of an IRB-approved clinical trial. These images were interpreted alongside images of liquid tissue-simulating phantoms that matched tissue optical properties. Variations in oxygenation and blood volume were mimicked in this way, and the data was used to interpret the clinical images. Impacts on Cherenkov emission spectra from tissue under these various conditions were also estimated. Results The presence of oxygenated vs deoxygenated blood in tissue has a visible impact on the color of Cherenkov emission, leading to a redder hue due to decreased attenuation of red wavelengths by oxyhemoglobin, similar to erythema or blush of tissue. This was verified in the tissue phantoms. Variations in blood concentration produce a strong blue-red trend in color space (R2 = 0.96), as verified by detailed analysis. Color Cherenkov images of right breast radiotherapy treatments displayed pink regions across the breast coincident with the treated area for all three patients, and the variations in color were interpreted relative to the phantom data. Conclusion This first investigation of color Cherenkov imaging uncovered the natural relationship between tissue composition and the spectral quality of emitted Cherenkov light. The correlation between blood content and color will be translated in future work to in vivo sensing of variations in fat and fibroglandular content in irradiated tissues. These findings will allow for the correction of Cherenkov images to produce accurate in vivo surface dose maps during patient treatments.

Purpose/Objective(s) Cherenkov imaging can uniquely record beam shapes directly on the patient, offering a brand new means of assessing patient position and treatment accuracy. We used Cherenkov imaging to assess accuracy of two patient positioning techniques, optical surfacing imaging versus traditional skin marks and room laser alignment (skin marks/lasers), during right breast irradiation. Materials/Methods All imaging data was obtained with IRB approval from patients receiving free-breathing, right breast radiation therapy with either 6X or 6X and 10X beams. Data was obtained from two separate clinics that utilize different positioning methods. Patients treated at one clinic were positioned using optical surface imaging and patients treated at a second clinic were positioned using skin marks/lasers. For each fraction imaged, DICE coefficient (% similarity) and MDC (mean distance to conformity) were measured by comparing Cherenkov imaging obtained for that fraction to the Cherenkov imaging from the initial fraction. A two-tailed t-test of unequal variance was performed to obtain P-values comparing MDC and DICE from the two positioning techniques. Results Cherenkov images taken of 127 fractions using optical surface imaging for breast setup and 47 fractions using skin marks/lasers setup showed that MDCs were found to average 2.02 mm (std dev of 0.83mm) and 2.47mm (std dev of 0.68mm), respectively, resulting in a P value of 0.07. The mean DICE coefficients averaged 97.33% (std dev of 1.13%) and 97.19% (std dev of 1.90%) for optical surface imaging and skin marks/lasers, respectively, with a P value of 0.65. The data confirms the null hypothesis in both cases. Conclusion Comparison of our Cherenkov image analytics from two centers, each using a separate positioning method (optical surface imaging and skin marks/lasers), revealed that there is no statistical difference in terms of MDC and DICE coefficient. This analysis confirms that both setup methods can be used confidently for patient positioning without compromising quality of care. This novel method for assessing alignment techniques is easy to use on a daily basis, adds no extra time or imaging dose to the patient, and analysis is automated, making this tool ideal for evaluating patient positioning for large numbers of treatments. Future work will examine different methods for alignment of more complex treatments such as deep-inspiration breath hold for left breast radiation.

Purpose/Objective(s) Cherenkov imaging is a novel technique that captures light emissions during radiation therapy, allowing for visualization of radiation treatments on patients, in real-time. We hypothesized that simply viewing the Cherenkov video images, both in real-time and with post-treatment review by radiation therapists, would identify events not previously reported in the existing QA program. Materials/Methods In December 2020, Cherenkov imaging cameras were introduced into an academic medical center with an existing QA program consisting of a hospital wide incident reporting system that is anonymous, voluntary, and non-punitive. Events are reviewed monthly by a multidisciplinary group including representatives from radiation therapy, dosimetry, nursing, physics and radiation oncologists. The Cherenkov cameras were installed in each treatment bunker, positioned laterally on each side of the couch. The cameras provided continuous, real-time video images of the patients and visualization of the irradiated tissue. Live viewing of the treatments was provided via a dedicated monitor in the console room. All treatments were imaged with the exception of treatments where optical surface imaging lights were on for SGRT. Results During this 3-month period, 12 events were reported in the hospital-based incident reporting system. Events were reviewed and categorized as 3 operational/process improvement (e.g., scheduling errors), 3 other safety events (e.g., patient falls), 3 treatment planning errors (e.g., wrong shifts calculated for setup), 1 prescription transcription error, 1 treatment delivery error (a missed treatment field), and 1 simulation error (suboptimal immobilization equipment used). Aside from a patient fall, all events were deemed to have no detectable harm to the patient. In this same time period, review of Cherenkov images identified 3 treatment delivery events, which were not identified by other means. The first was an AP-PA thoracic spine treatment and on one day, the treating therapists noted the patient's chin in the treatment field. Treatment was stopped, the patient was re-positioned for the remainder of the treatment. Second was an AP-PA lumbar spine field that on post-treatment review was noted that the patient's hands moved into the field. The third was a 3-field sacrum plan that on post-treatment review was noted that for 7 of 10 fractions, the patient's left arm was positioned over the exit RPO beam. Physics review estimated that the uninvolved arm received approximately 3 Gy. Conclusion Viewing of Cherenkov emission imaging by the treatment team identified delivery incidents due to non-ideal patient positioning during treatment and these events were not identified in the existing QA program. Future work will focus on determining incident rates detected by Cherenkov imaging and if this imaging can identify and/or avoid treatment delivery errors from reaching the patient. Automated detection and near real time notification of such events is a work in progress.

Purpose/Objective(s) Electron ultrahigh dose rate FLASH radiotherapy (UHDR/eFLASH-RT) is currently being extensively tested and modeled, and was studied in several rodent and large animal experiments and one clinical cancer patient. These studies suggest prospective dosimetry assessments are necessary to ensure safe delivery and widespread clinical translation of eFLASH-RT would clearly benefit from prior dose prediction and a treatment planning process that accounts for anatomical heterogeneity and complex geometries. In this study, a GAMOS Monte Carlo beam model was developed and implemented in a clinical treatment planning system for a modified UHDR electron LINAC to demonstrate eFLASH-RT planning of patients. Materials/Methods The gantry head was modelled without scattering foils or targets, representative of the LINAC modifications. Centered at the nominal energy of 10 MeV, the energy spectrum (σE) was varied to match the central axis percent depth dose (PDD) profiles of an open field measured with radiographic film. The beam's emittance cone angle (θcone) was determined by matching calculated and film measured lateral profiles, at several depths. The beam model and its configuration in the treatment planning system were validated with film measured lateral profiles and PDD's of the open field and nominal fields for clinical applicators. A GAMOS forward dose calculation was conducted for a mouse whole brain treatment and an eFLASH-RT plan was compared to a conventional electron plan for a human patient with a rib metastasis. Results Our eFLASH beam model agrees best with measurements at σE = 0.5MeV and θcone = 3.9o ± 0.2o. The model and its treatment planning system configuration were validated to clinically acceptable accuracy (the absolute average error was within 1.5% for in water lateral, 3% for in air lateral, and 2% for PDD's). The forward dose calculation showed dose was delivered to the entire mouse brain with adequate conformality (90% of the tumor volume receiving 90% of the prescribed dose). The comparison plans for the patient undergoing treatment for a rib metastasis demonstrated the capability to achieve an acceptable eFLASH-RT plan with routine accessories (90% of the tumor receiving 95% and 90% of the prescribed dose for eFLASH and conventional, respectively) in relatively complex geometry (right posterior oblique treatment with patient specific applicator cutout). Conclusion To the best of our knowledge, this study presents the first functional beam model commissioned in a clinical TPS for eFLASH-RT, enabling treatment planning and evaluation with minimal deviation from conventional radiotherapy workflow. By producing plans with the quality comparable to conventional plans, specifically for human patients involving complex geometries and tissue heterogeneity, the clinical translation of eFLASH-RT can be expedited. The open-source methods (described in https://github.com/mr3536/eFLASHBeamModeltoTPS ) can model other eFLASH irradiators with different beam characteristics.

High tissue pressures prevent chemotherapeutics from reaching the parenchyma of pancreatic ductal adenocarcinoma, which makes it difficult to treat this aggressive disease. Researchers currently use invasive probes to monitor the effectiveness of pressure-reducing therapies, but this practice introduces additional complications. Here, we hypothesize that Young’s modulus is a good surrogate for tissue pressure because collagen density and hyaluoronic acid, the key features of the tumor microenvironment responsible for high tissue pressures, also affect modulus elastograms. To corroborate this hypothesis, we used model-based quasi-static elastography to assess how the Young’s modulus of naturally occurring AsPc-1 pancreatic tumors varies with collagen density and hyaluoronic acid concentration. We observed that Young’s moduli of orthotopically grown xenograft tumors were 6 kPa (p < 0.05) higher than that of their subcutaneously grown counterparts. We also observed a strong correlation between Young’s modulus and regions within the tumors with high collagen (R2 ≈ 0.8) and hyaluoronic acid (R2 ≈ 0.6) densities. These preliminary results indicate that hyaluronic acid and collagen density, features of the pancreatic ductal adenocarcinoma tumor microenvironment responsible for high tissue pressure, influence Young’s modulus.

BackgroundAlthough aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy (PDT) is an effective FDA-approved therapy for actinic keratosis (AK), a substantial fraction of patients (up to 25%) do not respond to treatment. This study examined the feasibility of using pre-treatment measurements of PpIX concentration in AK lesions to predict response of ALA-PpIX PDT.MethodsA non-invasive fiber-optic fluorescence spectroscopy system was used to measure PpIX concentration in patients undergoing standard-of-care ALA-PDT for AK. All patients provided assessments of pain at the time of treatment (n=70), and a subset reported pain and erythema 48–76h after treatment (n=13).ResultsPpIX concentration was significantly higher in lesions of patients reporting high levels of pain (VAS score ≥5) immediately after treatment vs. patients reporting pain scores below VAS=5 (p

Rationale and Objectives It was hypothesized that perfusion computed tomography (CT), blood flow (BF), blood volume (BV), and vascular permeability surface area (PS) product parameters would be predictive of therapeutic anticancer agent uptake in pancreatic cancer, facilitating image-guided interpretation of human treatments. The hypothesis was tested in an orthotopic rabbit model of pancreatic cancer, by establishing the model, imaging with endoscopic ultrasound (EUS) and contrast CT, and spatially comparing the perfusion maps to the ex vivo uptake values of the injected photosensitizer, verteporfin. Materials and Methods Nine New Zealand white rabbits underwent direct pancreas implantation of VX2 tumors, and CT perfusion or EUS was performed 10 days postimplantation. Verteporfin was injected during CT imaging, and the tissue was removed 1 hour postinjection for frozen tissue fluorescence scanning. Region-of-interest comparisons of CT data with ex vivo fluorescence and histopathologic staining were performed. Results Dynamic contrast-enhanced CT showed enhanced BF, BV, and PS in the tumor rim and decreased BF, BV, and PS in the tumor core. Significant correlations were found between ex vivo verteporfin concentration and each of BF, BV, and PS. Conclusions The efficacy of verteporfin delivery in tumors is estimated by perfusion CT, providing a noninvasive method of mapping photosensitizer dose.

Rationale and Objectives Near-infrared spectroscopy (NIRS) of breast can provide functional information on the vascular and structural compartments of tissues in regions identified during simultaneous magnetic resonance imaging (MRI). NIRS can be acquired during dynamic contrast-enhanced MRI (DCE-MRI) to accomplish image-guided spectroscopy of the enhancing regions, potentially increasing the diagnostic specificity of the examination and reducing the number of biopsies performed as a result of inconclusive MRI breast imaging studies. Materials and Methods We combine synergistic attributes of concurrent DCE-MRI and NIRS with a new design of the clinical NIRS breast interface that couples to a standard MR breast coil and allows imaging of variable breast sizes. Spectral information from healthy volunteers and cancer patients is recovered, providing molecular information in regions defined by the segmented MR image volume. Results The new coupling system significantly improves examination utility by allowing improved coupling of the NIR fibers to breasts of all cup sizes and lesion locations. This improvement is demonstrated over a range of breast sizes (cup size A through D) and normal tissue heterogeneity using a group of eight healthy volunteers and two cancer patients. Lesions located in the axillary region and medial-posterior breast are now accessible to NIRS optodes. Reconstructed images were found to have biologically plausible hemoglobin content, oxygen saturation, and water and lipid fractions. Conclusions In summary, a new NIRS/MRI breast interface was developed to accommodate the variation in breast sizes and lesion locations that can be expected in clinical practice. DCE-MRI–guided NIRS quantifies total hemoglobin, oxygenation, and scattering in MR-enhancing regions, increasing the diagnostic information acquired from MR examinations.

Fluorescence sampling of cellular function is widely used in all aspects of biology, allowing the visualization of cellular and sub-cellular biological processes with spatial resolutions in the range from nanometers up to centimeters. Imaging of fluorescence in vivo has become the most commonly used radiological tool in all pre-clinical work. In the last decade, full-body pre-clinical imaging systems have emerged with a wide range of utilities and niche application areas. The range of fluorescent probes that can be excited in the visible to near-infrared part of the electromagnetic spectrum continues to expand, with the most value for in vivo use being beyond the 630 nm wavelength, because the absorption of light sharply decreases. Whole-body in vivo fluorescence imaging has not yet reached a state of maturity that allows its routine use in the scope of large-scale pre-clinical studies. This is in part due to an incomplete understanding of what the actual fundamental capabilities and limitations of this imaging modality are. However, progress is continuously being made in research laboratories pushing the limits of the approach to consistently improve its performance in terms of spatial resolution, sensitivity and quantification. This paper reviews this imaging technology with a particular emphasis on its potential uses and limitations, the required instrumentation, and the possible imaging geometries and applications. A detailed account of the main commercially available systems is provided as well as some perspective relating to the future of the technology development. Although the vast majority of applications of in vivo small animal imaging are based on epi-illumination planar imaging, the future success of the method relies heavily on the design of novel imaging systems based on state-of-the-art optical technology used in conjunction with high spatial resolution structural modalities such as MRI, CT or ultra-sound.

Rationale and Objectives Noninvasive molecular imaging of glioma tumor receptor activity was assessed with diagnostic in vivo fluorescence monitoring during targeted therapy. The study goals were to assess the range of use for treatment monitoring and stratification of tumor types using epidermal growth factor (EGF) receptor (EGFR) status with administration of fluorescently labeled EGF and determine its utility for tumor detection compared to magnetic resonance imaging (MRI). Materials and Methods EGFR+ and EGFR− glioma tumor lines (human glioma [U251-GFP] and rat gliosarcoma [9L-GFP], respectively) were used to assess these goals, having a 20-fold difference between their EGF uptakes. Results Treatment with cetuximab in the EGFR+ tumor-bearing animals led to decreased EGF tumor uptake, whereas for the EGFR− tumors, no change in fluorescence signal followed treatment. This diagnostic difference in EGFR expression could be used to stratify the tumor-bearing animals into groups of potential responders and nonresponders, and receiver-operating characteristic curve analysis revealed an area under the curve (AUC) of 0.92 in separating these tumors. The nonlocalized growth pattern of U251-GFP tumors resulted in detection difficulty on standard MRI, but high EGFR expression made them detectable by fluorescence imaging (AUC = 1.0). The EGFR+ U251-GFP tumor–bearing animals could be noninvasively stratified into treated and untreated groups on the basis of fluorescence intensity difference ( P = .035, AUC = 0.90). Conclusions EGFR expression was tracked in vivo with fluorescence and determined to be of use for the stratification of EGFR+ and EGFR− tumors, the detection of EGFR+ tumors, and monitoring of molecular therapy.

Purpose: To compensate for photosensitizer uptake variation in photodynamic therapy (PDT), via control of delivered light dose through photodynamic dose calculation based on online dosimetry of photosensitizer in tissue before treatment. Methods and Materials: Photosensitizer verteporfin was quantified via multiple fluorescence microprobe measurements immediately before treatment. To compensate individual PDT treatments, photodynamic doses were calculated on an individual animal basis, by matching the light delivered to provide an equal photosensitizer dose multiplied by light dose. This was completed for the lower quartile, median, and upper quartile of the photosensitizer distribution. PDT-induced tumor responses were evaluated by the tumor regrowth assay. Results: Verteporfin uptake varied considerably among tumors and within a tumor. The coefficient of variation in the surviving fraction was found significantly decreased in groups compensated to the lower quartile (CL-PDT), the median (CM-PDT), and the upper quartile (CU-PDT) of photosensitizer distribution. The CL-PDT group was significantly less effective compared with NC-PDT (Noncompensated PDT), CM-PDT, and CU-PDT treatments. No significant difference in effectiveness was observed between NC-PDT, CM-PDT, and CU-PDT treatment groups. Conclusions: This research suggests that accurate quantification of tissue photosensitizer levels and subsequent adjustment of light dose will allow for reduced subject variation and improved treatment consistency.

Materials and Methods. A new spectral reconstruction method that is considered to provide the most accurate estimates of hemoglobin level, oxygen saturation, water fraction, scattering power, and amplitude was used to assess healthy breast tissue imaged in vivo by means of NIR tomography. The approach directly recovers functional parameters with inherent inclusion of spectral behavior enforced through the incorporation of a priori model assumptions. Sixty subjects were imaged by using a frequency-domain instrument followed by spectral image reconstruction and statistical analysis for significant correlations. Results. The new analysis shows statistically significant inverse correlations between body mass index and breast total hemoglobin and water fractions. Water fraction also correlated inversely with age and separated certain categories of breast density. Average scatter power was indicative of breast radiographic density composition, whereas scatter amplitude varied inversely with breast diameter. Total hemoglobin correlated with water fraction, whereas water correlated with scatter power. Conclusion. The changes observed here are attributable to volume fraction alterations and provide some of the most comprehensive data on breast composition variations with demographic factors.

Cerenkov light emission from MeV gamma-ray and electron beam delivery has recently been shown to be detectable and could be used in some applications for 3D dosimetry in radiation therapy in water tanks or 2D surface dosimetry in humans. The major potential benefit of Cerenkov imaging is that it is a way to image beams in real time with several frames per second. As such, it is feasible to image treatment beams dynamically, and create composite visualizations of the treatment plans. This imaging can be used to verify new treatment plans prior to application to patients, or to quickly verify new machines, or testing in situations where access is limited.

In this study, the vascular and tissue oxygen changes induced by photodynamic therapy in the RIF-1 tumor were examined, using electron paramagnetic resonance (EPR) oximetry. Two photosensitizers, including verteporfin (BPD-MA in a lipid-based formulation) and aminolevulinic acid-induced protoporphyrin IX (ALA-PPIX), were investigated with optical irradiation, sufficient to induce sub-curative damage in the tumor tissue, and the transient changes in PO(2) and vascular perfusion were examined. A large increase in tissue oxygenation (from 3 up to 9.5 mmHg) was observed when treated with ALA-PPIX based photodynamic therapy, which lasted during the treatment and a small residual increase that returned back to baseline levels by 48 h after treatment. With verteporfin-based photodynamic therapy, one group of animals was irradiated 15 min after injection and exhibited a small decrease in oxygenation relative to pre-irradiation levels. The second group was irradiated at 3 h after injection and exhibited a large increase in the average PO(2), (from 3 to 15 mmHg) by the end of the treatment. These observations indicate that photodynamic therapy significantly increases tissue PO(2) under certain treatment conditions, with the potential cause being either increased local blood flow or decreased local oxygen metabolic consumption due to cellular damage.

Diagnostic tools to noninvasively measure tissue function are still relatively limited, and the development of new contrast agents that will provide information about vascular leakage are one of the most robust measurements possible. Near-infrared (NIR) measurements from tissue have significant potential to displace x-ray or nuclear medicine scans in these types of applications, yet NIR has distinctly different strengths and weaknesses relative to standard clinical tools. The key challenges for NIR methods to progress into clinical use are threefold; first, measurement methods must be developed that are insensitive to tissue surface effects and shape; second, the technology (both hardware and software) must mature to the point at which physicians are comfortable with lower resolution images or superposition of images on other clinical modalities or simply using numbers to quantify emission intensity; and third, there is a need to develop commercially available function-specific dyes that can be used in humans to probe surrogate markers of the disease or, ideally, molecular signatures of the disease. Significant strides have been made in these areas, and much more can be expected from NIR if all are advanced together. In this issue of Academic Radiology, the report by Fischer et al (1) demonstrates a key innovation in the latter area through evaluation of tissue function by using a combination of two dyes that have very different binding kinetics to plasma proteins and therefore very different effective molecular weights and charges. This study presents a pilot analysis of how inflammation of the vessels in arthritis can be imaged with vascular permeability probes, and, in

Water content and sebum amount of irradiated and non-irradiated stratum corneum was measured by corneometer and sebumeter on the first and last day of RT, at 2 weeks, 4 weeks, and 3 months after RT. Sebum composition was analyzed by chromatography. Symptoms (pain and pruritus) were measured by Visual Analog Scale (VAS) and signs (erythema, dryness, and desquamation) were graded blind by a dermatologist. Eligibility criteria included women aged between 30 to 65 years and no surgical resection in the measurement site. The primary endpoint was the water content recovery rate between Weeks 2 and 4 post-RT (B vs C). The recovery rate was analyzed by Wilcoxon signed-rank test. Results: Seventy-six patients were analyzed. On the last day of RT and at 2 weeks post RT, water content was significantly decreased in group B (n Z 30) and C (n Z 32) vs A (n Z 14) (p < 0.05). At 4 weeks post RT, water content in group B returned to pre RT levels without significantly difference from group A (P Z 0.70), and reduction in water content was sustained in group C (p < 0.05). At 3 months post RT, the differences between three groups were not statistically significant. No adverse effects related to a moisturizer were noted. The water content recovery rate between Weeks 2 4 was significantly improved in group B vs C (0.242 vs 0.055, p < 0.05). The sebum amount and proportion of wax ester were markedly decreased in both irradiated and non-irradiated side after RT. The decrease of sebum sustained to 3 months post RT in irradiated side. Pain VAS score was improved in group A vs C on the last day of RT (p < 0.05) and in group B vs C at 3 months post-RT (p < 0.05). No difference was found on pruritus. Dryness and desquamation were significantly improved with moisturizer application (p < 0.05), but no effect on erythema. Conclusions: RT significantly reduced stratum corneum water content and induced quantifiable persistent sebaceous gland damage. Two week treatment of a heparinoid moisturizer after RT effectively improved RT-induced skin dryness. The prophylactic application of a moisturizer prevented severe skin dryness and can improve symptoms related to RD. Author Disclosure: M. Ogita: None. K. Sekiguchi: None. K. Akahane: None. J. Kawamori: None. R. Ito: None. C. Haga: None. S. Arai: None. O. Takahashi: None.

meaning no overlap if 0 and 100% concordance if 1. Paired samples t-test was performed to evaluate the changes in breast volumes. Results: The median interval between two scans was 90 days (range, 14170 days). Median age was 44 years (range, 29-69 years). The tumor was situated in the upper outer, retroareolar, lower outer, and lower inner quadrants in 16, 2, 2, and 2 patients, respectively. In 7 cases multifocality was present. Seven patients had excisional biopsy before the preoperative CT. Median pre and postoperative breast CTVs were 442 cc (range, 2761061 cc) vs 516 cc (range, 243-917 cc), respectively (p Z 0.132). A median of 4 surgical clips (range, 2-6) were inserted during the surgery. Median preoperative tumor volume and postoperative lumpectomy cavity volumes were 6.6cc (range, 0.4-49 cc) and 22.95 cc (range, 6.2-102.2 cc), respectively. Median CI was 0.07 (in 5 cases 1, and in 8 cases 0). Median shifts between the center of volumes were 1.02 cm (range, 0.4-4.43 cm) in x, 1.07cm (range, 0.05-5.67 cm) in y, and 1.12cm (range, 0-3.75 cm) in z directions. Conclusions: Our study shows that the tumor bed is remarkably replaced after oncoplastic surgery with latissimus dorsi mini-flaps. Only in 5 of 22 cases, preoperative tumor bed and postoperative lumpectomy cavity were fully superposed. In remaining cases there were remarkable shifts between two volumes. Special care should be given for defining lumpectomy cavity in radiation therapy planning. Author Disclosure: G. Alco: None. S. Igdem: None. S. Okkan: None. M. Dincer: None. F. Agacayak: None. D. Selamoglu: None. S. Ilgun: None. V. Ozmen: None.