Fiber-optics based fluorescence detection. Part I: Basic concepts.

Continuous in-line detection and process monitoring are essential for industrial, analytical, and biomedical applications. Lightweight, highly flexible, and low-cost fiber optics enable the construction of compact and robust hand-held devices for in situ chemical and biological species analysis in both industrial and biomedical in vitro/in vivo detection. Despite the broad range of fiber-optic based applications, we lack a good understanding of the parameters that govern the efficiency of light collection or the sensitivity of detection. Consequently, comparing samples of different optical density and/or geometry becomes challenging and can lead to misinterpretation of results; especially when we lack the approaches necessary to correct the detected signal (spectra) for artifacts such as inner-filter effect or scattering. Hence, in this work, we discuss factors affecting the signal detected by the fiber optic in the bare and lens-coupled flat-tipped configurations that lead to signal/spectral distortions. We also present a simple generic model describing the excitation profile and emission collection efficiency that we verify with experimental data. Understanding the principles governing the signal collected by the fiber will provide rationales for correcting the measured emission spectra and recovering the true emission profile of optically dense samples.

Photophysical properties of DAPI in PVA films. Possibility of room temperature phosphorescence.

We studied the spectral properties of 4'-6-diamidino-2-phenylindole (DAPI) in poly (vinyl alcohol) (PVA) films. Absorption and fluorescence spectra, emission and excitation spectra, quantum yield, and fluorescence lifetime have been characterized. An efficient room temperature phosphorescence (RTP) of DAPI has been observed with UV and blue light excitations. A few hundred millisecond phosphorescence lifetime enables a gated detection with sufficient background reduction. We found the phosphorescent Quantum Yield of DAPI in PVA Film to be 0.0009.

Effect of annealing on the room temperature luminescence of coumarin 106 in PVA films.

We studied the effect of annealing on the luminescence of Coumarin 106 (C106) in poly (vinyl alcohol) films (PVA films). The samples and reference polymer films were treated at temperatures between 100 °C and 150 °C (212 F and 302 F) for various times. After cooling and smoothing, the samples and references were measured at room temperature. We observed that the PVA polymer (reference films) changes its optical properties with annealing at higher temperatures, affecting the baselines in absorption and the backgrounds in emission measurements. This requires precise background subtractions and control of the signal-to-noise ratio. Whereas the fluorescence intensity of C106 in PVA films modestly decreases with annealing, the phosphorescence depends dramatically and progressively increases by many folds. The fluorescence quantum yields and lifetimes decrease with the annealing, which suggests an increase in the non-radiative processes in the singlet excited state S1. The increase in the phosphorescence intensities results from increased intersystem crossing (ISC), which also decreases fluorescence. We also studied the effect of annealing on phosphorescence with the directly excited triplet state of C106. In this case, two processes are affected by annealing, S0→T1absorption and T1→S0phosphorescence. The long-wavelength excitation (475 nm) avoids PVA polymer excitation. The phosphorescence lifetime decreases with annealing while the phosphorescence intensity increases. These changes suggest that the radiative rate of T1→ S0increases with annealing.

Room Temperature Phosphorescence of 5,6-Benzoquinoline.

Phosphorescence emission of 5,6-Benzoquinoline embedded in poly (vinyl alcohol) film has been studied at room temperature. A strong green long-lived emission was observed in films doped with 5,6-Benzoquinoline while illuminated on a UV plate. A broad phosphorescence emission spectrum is centered at about 500 nm. The phosphorescence excitation spectrum follows the absorption spectrum of 5,6-Benzoquinoline, except for a long-wavelength part, which is well beyond the absorption band. This long-wavelength part of the absorption spectrum is responsible for the forbidden S0-T1transition. The excitation at 430 nm resulted in the long-lived emission with a spectrum similar to the phosphorescence spectrum obtained with UV excitation within the absorption of 5,6-Benzoquinoline. The phosphorescence anisotropy obtained with a direct S0-T1excitation is positive, while the UV excitation is negative. In contrast to fluorescence, the phosphorescence intensity strongly depends on temperature. Phosphorescence lifetimes with UV and long-wavelength excitation are similar, with a mean value of about 0.5 s.

Room temperature phosphorescence of 2-aminopyridine with direct triplet state excitation.

Phosphorescence emission at room temperature has been observed from 2-Aminopyridyne (2APi) embedded in poly (vinyl alcohol) (PVA) films. The gated emission with UV excitation at 305 nm results in a residual delayed fluorescence at around 350 nm and a broad phosphorescence spectrum with a maximum of around 500 nm. The phosphorescence excitation spectrum of 2APi - doped PVA film differs from the absorption spectrum in the long-wavelength part, showing a band at about 400-450 nm. The phosphorescence spectrum measured with a blue (420 nm) excitation closely resembles the spectrum measured with 305 nm excitation. Whereas the phosphorescence anisotropy measured with UV excitation is low and negative, with the blue excitation, the anisotropy is high and positive. The phosphorescence lifetimes (a fraction of a millisecond) are similar for UV and blue excitations. Both phosphorescence emissions with either UV or blue excitation strongly depend on temperature.

Lung Cancer Screening Registry Reveals Low-dose CT Screening Remains Heavily Underutilized.

BACKGROUND: Since 2013, the United States Preventive Services Task Force has recommended annual screening for lung cancer in high-risk patients with low-dose computed tomography (LDCT). Current literature has provided estimates of the lung cancer screening rate and only prior to appropriate insurance coverage for LDCTs. The aim of this study was to use newly established registry data to assess the lung cancer screening rate across the United States. MATERIALS AND METHODS: Using data from the Lung Cancer Screening Registry provided by the American College of Radiology in 2016, we collected the total number of LDCT screens performed from all 1962 accredited radiographic screening sites. The 2015 National Health Interview Survey was used to estimate screening eligible smokers per United States Preventive Services Task Force criteria. These data were compared to calculate screening rate. RESULTS: In 2016, 2.0% of 7.6 million eligible smokers were screened. Rates varied by region from 1.1% in the West to 3.9% in the Northeast. The South consisted of 40.4% of eligible smokers and the most accredited screening sites (37%); however, their screening rate was among the lowest (1.7%) in the nation. Smoking cessation counseling was offered to 84% of screened current smokers prior to receiving LDCTs. CONCLUSIONS: Lung cancer screening remains heavily underutilized despite guideline recommendation since 2013, insurance coverage, and its potential to prevent thousands of lung cancer deaths annually.

Treatment Timing in Small Cell Lung Cancer, a National Cancer Database Analysis.

OBJECTIVES: Small cell lung cancer (SCLC) is an aggressive disease treated as soon as possible given its rapid doubling time. Evidence for the appropriate time to chemotherapy initiation (TCI) for SCLC is lacking. This study evaluated TCI in SCLC on a national level. MATERIALS AND METHODS: The National Cancer Database identified 64,491 SCLC patients treated with chemotherapy from 2010 to 2014. Factors associated with TCI were identified with multiple linear regression analyses. TCI was categorized into 4 groups using cutoff points of 7, 14, and 28 days. Using these categories, median overall survival and log-rank test was used for univariate analysis of the survival outcome and the Cox model was used for multivariate analysis. RESULTS: Median TCI was 18 days with 21% treated ≤7 days, 21% in 8 to 14 days, 30% 15 to 28 days, and 28% >28 days from diagnosis. Younger age, white race, no insurance, more comorbidities, and higher stage were associated with shorter TCI. Median overall survival for TCI within 7 days was 8.2 months, 8 to 14 days was 9.2 months, 15 to 28 days was 10.3 months, and > 28 days was 10.8 months (P<0.001). In the multivariate analysis, increased TCI was associated with improved survival across all stages. Among stage IV patients, compared with TCI≤7 days, the hazard ratio (HR) is 0.92 (P<0.001) for 8 to 14 days, HR 0.82 (P<0.001) for 15 to 28 days, and HR 0.77 (P<0.001) for >28 days of TCI. Results were similar for stage III and for stages I+II. CONCLUSIONS: Our results show worse survival with shorter TCI. This provides evidence to inform a discussion regarding appropriate treatment timing and individualizing treatment.

NSCLC patient "migration" for treatment: A retrospective analysis of patient characteristics, travel patterns, and survival differences.

PURPOSE: Every year a significant population exists of those diagnosed with nonsmall cell lung cancer (NSCLC) who do not receive initial treatment upon diagnosis and then "migrate" to additional hospital before ultimately getting treatment. Migration to different hospitals may play a role in the decision to treat or not-to-treat, and we aimed to evaluate the potential factors that lead to treatment. METHODS: A retrospective review of 6212 patients with NSCLC from 29 Kentucky hospital registries from 2012 to 2014 was performed. Variables collected included hospital accreditation status, age at diagnosis, stage, overall survival (OS), and insurance status. Hospital records were matched to Kentucky Cancer Registry records to determine the number of hospitals visited for treatment. RESULTS: Most patients were treated at their initial hospital (73%). Of the remaining patients, 36% migrated to a different hospital where most received treatment (93%). Migrating to another hospital was associated with Stage I-III disease, younger age (66.4 vs 72.2 years), and longer OS (561 vs 157 days). Notably, migration was also associated with private insurance status and missing treatment modalities at the initial hospital. Treatment after migrating was associated with Stage I-II disease, younger age (65.8 vs 72.8 years), and longer OS (595 vs 153 days). After adjusting for confounders, treated migrating patients lived longer than initially treated patients (591 vs 505 days), especially among those with stage III (563 vs 495 days) and IV (379 vs 300 days) disease. CONCLUSION: This analysis demonstrates a survival benefit for initially untreated patients with advanced disease who migrate to another hospital for treatment. Migration was associated with having private insurance, thus making it noteworthy of the relationship between NSCLC survival benefit and insurance status.

Performance of community-based lung cancer screening program in a Histoplasma endemic region.

OBJECTIVES: Lung cancer screening with low dose computed-tomography (LDCT) is currently recommended for high-risk populations based on mortality benefit shown in the National Lung Screening Trial (NLST). This study evaluated performance of a community-based lung cancer screening program in a Histoplasma endemic region. MATERIALS AND METHODS: Demographic and clinical information was collected through retrospective review of patients in the Lung Cancer Screening program of a Kentucky (Histoplasma endemic region) health system from 2016 and 2017. A positive LDCT screen is defined as Lung-RADS version 1.0 assessment categories 3 or 4. Patients characteristics, initial screening results and follow up were analyzed and compared to NLST results. RESULTS: A total of 4500 LDCT screens were performed in 2016 (39%) and 2017 (61%) with 43% adherence rate to repeat annual screen in 2017. Mean age of patients was 64 years, with majority being females (54%) and current smokers (69%) with average 52-pack year smoking history. The rate of positive LDCT was 13.3% (600) varying based on baseline (14.6%) and annual (9.5%) screen. A total of 70 lung cancers were diagnosed among all positive LDCT screens (11.7%) with a false positive rate of 12%. CONCLUSIONS: Baseline positive screens in our study are similar to NLST data with Lung-RADS criteria implementation (14.6% vs 13.6%, p = 0.15) despite being a Histoplasma endemic region. Our study shows a successful performance of a community-based lung cancer screening program in a Histoplasma endemic region.

Timing of treatment in small-cell lung cancer.

Small-cell lung cancer (SCLC) is an aggressive disease with poor survival and rapid doubling time. Current practice is to treat SCLC as soon as possible but evidence on appropriate timing of treatment from diagnosis (TTD) is lacking. This is a retrospective analysis of SCLC patients from the 2012 to 2015 Kentucky Cancer Registry. Data collected included age at diagnosis, stage, gender, race, insurance and treatment. Factors and survival associated with TTD were identified with logistic regression analyses and Cox proportional hazards models. Among the 2992 SCLC patients, 2371 (79%) of SCLC patients were treated with one or more treatment modalities. Among treated patients, 93% received chemotherapy ± radiation with the mean TTD of 18 days. Most patients (80%) have TTD of ≤ 4 weeks with 33% treated within 1 week, 20% 1-2 weeks, and 27% 2-4 weeks from diagnosis. Delay in treatment (TTD > 4 weeks) was less in stage III and IV disease (odds ratio: 0.33 and 0.27 respectively, p < 0.01) but not significantly associated with age, race, gender, and insurance. One and two-year survival of patients with TTD ≤ 4 weeks was significantly worse when compared to > 4 weeks (hazard ratio = 1.43, 95% CI 1.2-1.6, p < 0.01; HR = 1.45, 95% CI 1.3-1.6, p < 0.01 respectively). These results show a trend toward better survival with late treatment of SCLC. Therefore, a general urgency to treat SCLC needs to be re-evaluated with consideration of patients needing more optimization before treatment. Further studies are needed to better clarify the appropriate timing of treatment from diagnosis in SCLC and who will benefit from early versus late treatment.

Laser targeting with C-arm fluoroscopy: effect on image acquisition and radiation exposure.

OBJECTIVES: Reducing unnecessary radiation exposure from medical imaging is paramount. This study assessed whether a laser aiming guide for C-arm fluoroscopy reduced the number of exposures needed to obtain an acceptable image, thereby reducing total fluoroscopy time for hip, knee, and ankle fluoroscopy. METHODS: An obese cadaver was placed supine on a radiolucent surgical table. Images were obtained by licensed radiologic technologists using a calibrated OEC 9900 Elite C-arm with laser targeting (LT) and without LT (NLT). Dosimeters were placed 1, 3, and 6 ft (30.5, 91.5, and 183 cm) away from the center of the C-arm at 90-degree angles at 2 levels, simulating thyroid and gonadal exposure. Posterior-anterior (PA) images of the bilateral lower extremities were obtained with each technician acquiring 24 centered images (hip, knee, and ankle) using both LT and NLT C-arm fluoroscopy. RESULTS: Total fluoroscopy time was reduced by 19% when using LT with a 39% reduction for the knee and a 29% reduction for the ankle. The addition of LT improved the likelihood of obtaining a centered image for knees and ankles but not for hips. The gonadal dosimetry data were significantly higher than the thyroid dosimetry badges at 1 ft. At the 3-ft zone, only trace amounts of radiation were detected; the 6-ft zone reported no radiation exposure in either group. CONCLUSIONS: LT helped with imaging knees and ankles with statistically significant reductions in fluoroscopy time and a statistically significant improvement of image quality defined as obtaining a centered PA image faster. The dosimetry badges detected minimal exposure at 3 ft and no detectable exposure at 6 ft at both levels.