A paper-based chemical tongue based on the charge transfer complex of ninhydrin with an array of metal-doped carbon dots discriminates natural amino acids and several of their enantiomers.

Simultaneous detection of multiple amino acids (AAs) instead of individual AAs is inherently worthwhile for improving diagnostic accuracy in clinical applications. Here, a facile and reliable colorimetric microfluidic paper-based analytical device (µPAD) using carbon dots doped with transition metals (Cr3+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, and Zn2+) has been provided to detect and discriminate 20 natural amino acids. To make the colourless metal-doped carbon dots suitable for colorimetric assays, they were mixed with ninhydrin to form a charge transfer complex. This optical tongue system, which was constructed by dropping mixtures of ninhydrin with a series of metal-doped carbon dots on a paper substrate in an array format, represented obvious but different colorimetric signatures for every examined amino acid. Since bovine serum albumin was used as a chiral selector reagent for synthesizing the CDs, the sensor device represented excellent selectivity to identify enantiomeric species of AAs. This is the first optical array device that can simultaneously discriminate AAs and several of their enantiomers. We employed various statistical and chemometric methods to analyze the digital data library collected by Image J software, including principal component analysis (PCA), linear discriminant analysis (LDA), and hierarchical cluster analysis (HCA). Twenty AAs could be well distinguished at various concentrations (10.00, 5.00, 2.50, and 1.25 mM). The colorimetric patterns were highly repeatable and were characteristic of individual AAs. Besides qualitative analysis, the designed µPAD-based optical tongue represented quantitative analysis ability, e.g., for lysine in the concentration ranges of 0.005-20.0 mM with a detection limit of 1.0 × 10-6 M and for arginine in the concentration range of 0.12-20.00 mM with a detection limit of 80.0 × 10-6 M. In addition, the binary, ternary, and quaternary mixtures of AAs could also be well recognized with this sensor.

A poly(arylene ethynylene)-based microfluidic fluorescence sensor array for discrimination of polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are persistent contaminants in the environment. Several of them have carcinogenic properties. There is considerable interest in their sensitive low-cost detection and monitoring. We present a simple paper-based microfluidic sensor for the rapid detection of PAHs. Craft punch patterning generated multiple detection zones inhabited by fluorescent poly(arylene ethynylene)s (PAEs). Changes in fluorescence image and/or intensity of the sensor array were recorded using a smartphone camera. The RGB color values of the photographed images were extracted through ImageJ software. 10 different PAHs were correctly identified using Principal Component Analysis and discrimination analysis (PCA-DA). 100% classification accuracy was achieved for model training, whereas validating the PCA-DA model by cross-validation resulted in 93% classification accuracy for 5.0 mg L-1 analyte.

A 3D origami paper-based analytical device combined with PVC membrane for colorimetric assay of heavy metal ions: Application to determination of Cu(II) in water samples.

Microfluidic paper-based analytical devices (µPADs) as a potentially powerful analytical platform have recently gained significant attention for on-site monitoring of heavy metal ions, which are one of the most significant environmental concern because of non-degradability and high toxicity. The commonly applied µPADs suffers from some defects, such as heterogeneous deposition of reagent, resulting in poor detection limits and low sensitivity. So, in this work, a three-dimensional origami µPAD combined with PVC Membrane was developed, which can manage problems of movement of colored products or leaching out the dye and leading to color heterogeneity in the detection zones. Furthermore, a waste layer was added to µPAD for loading of more amounts of the analyte, which results in improvement of detection limit. As a proof of concept, the µPAD was used for the analysis of Cu2+ ion. For this purpose, pyrocatechol violet and chrome azurol S as colorimetric reagents were doped into PVC membrane and injected in the detection zone. The proposed µPAD was presented good linearity in the ranges of 5.0-1400.0 and 5.0-200.0 mg L-1, and the limits of detections of 1.7 and 1.9 mg L-1 in presence of chrome azurol S and pyrocatechol violet, respectively.

A Green Chemosensor for Colorimetric Determination of Phosphate Ion in Soil, Bone, and Water Samples Using Curcumin Nanoparticles.

This article presents a sensitive and straightforward colorimetric chemosensor for the determination of phosphate ion utilizing curcumin nanoparticles (CUNPs) as the sensing system. The color of as-prepared CUNPs can be changed from yellow to orange upon adding iron(III) ions due to the formation of a complex with CUNPs. However, in the presence of phosphate ions, iron(III) ions prefer to bind to phosphate ions and, subsequently the color of CUNPs is selectively recovered because of releasing the iron(III) ions from the CUNPs-iron(III) complex. Therefore, in this work the selective color changing of the CUNPs-iron(III) system upon the addition of phosphate ions was used for the quantitative sensing of phosphate ions. Various factors, such as the pH, concentration of iron(III) and volume of CUNPs, were examined and the optimum conditions were established. A linear calibration graph over the range of 10 - 400 ng mL-1 for phosphate (r = 0.9995) was achieved using the optimal conditions. The limit of detection (LOD) of the proposed method for phosphate was 7.1 ng mL-1 and the relative standard deviation (RSD) for measuring 50 ng mL-1 of phosphate was 3.7% (n = 8). The developed method was applied for the measurement of phosphate in water, soil, and bone samples. Satisfactory results were obtained.

Four-dimensional computed tomography-based biomechanical measurements of pulmonary function and their correlation with clinical outcome for lung stereotactic body radiation therapy patients.

BACKGROUND: Functional image guided radiotherapy allows for the delivery of an equivalent dose to tumor targets while sparing high ventilation lung tissues. In this study, we investigate whether radiation dose to functional lung is associated with clinical outcome for stereotactic body radiation therapy (SBRT) patients. METHODS: Four-dimensional computed tomography (4DCT) images were used to assess lung function. Deformable image registration (DIR) was performed from the end-inhale phase to the end-exhale phase with resultant displacement vectors used to calculate ventilation maps. In addition to the Jacobian-based ventilation we introduce a volumetric variation method (Rv) based on a biomechanical finite element method (FEM), to assess lung ventilation. Thirty NSCLC patients, treated with SBRT, were evaluated in this study. 4DCT images were used to calculate both Jacobian and Rv-based ventilation images. Areas under the receiver operating characteristic curve (AUC) were used to assess the predictive power of functional metrics. Metrics were calculated over the whole lung as well as high and low ventilated regions. RESULTS: Ventilation in dose regions between 1 and 5 Gy had higher AUC values compared to other dose regions. Rv based ventilation imaging method also showed to be less spatially variant and less heterogeneous, and the resultant Rv metrics had higher AUC values for predicting grade 2+ dyspnea. CONCLUSIONS: Low dose delivered to high ventilation areas may also increase the risk of compromised pulmonary function. Rv based ventilation images could be useful for the prediction of clinical toxicity for lung SBRT patients.

4-Dimensional computed tomography-based ventilation and compliance images for quantification of radiation-induced changes in pulmonary function.

INTRODUCTION: 4-Dimensional computed tomography (4DCT)-based ventilation imaging is a promising technique for evaluating pulmonary function, but lung elasticity and mechanics are usually not part of the ventilation image analysis. In this study we demonstrate a 4DCT-based imaging technique that can be used to calculate regional lung compliance changes after radiotherapy (RT). METHODS: Six lung cancer patients were included in this study. Four of the patients had 4DCT images acquired pre-RT, 3 and 9 months post-RT. Ventilation and compliance were calculated from the deformable image registration (DIR) of 4DCTs, performed from the end-inhale to the end-exhale breathing phase. Regional compliance was defined as the ratio of volumetric variation and associated stress in each voxel, representing lung elasticity and computed using a FEM-based framework. Ventilation, compliance and CT density were calculated for all pre-RT and post-RT 4DCTs and evaluation metrics were computed. RESULTS: Average CT density changes were 13.6 ± 11.4HU after 3 months and 26.9 ± 15.8HU after 9 months. Ventilation was reduced at 3 months, but improved at 9 months in regions with dose ≥ 35 Gy, encompassing about 10% of the lung volume; compliance was reduced at both time-points. Radiation dose ≥ 35 Gy caused major change in lung density and ventilation, which was higher than that previously reported in the literature (i.e. 24 Gy). CONCLUSION: Lung tissue response is diverse with respect to CT density, ventilation and compliance. Combination of ventilation and compliance with CT density could be beneficial for understanding radiation-induced lung damage and consequently could help develop improved treatment protocols for lung cancer patients.

Utilization of a hybrid finite-element based registration method to quantify heterogeneous tumor response for adaptive treatment for lung cancer patients.

Tumor response to radiation treatment (RT) can be evaluated from changes in metabolic activity between two positron emission tomography (PET) images. Activity changes at individual voxels in pre-treatment PET images (PET1), however, cannot be derived until their associated PET-CT (CT1) images are appropriately registered to during-treatment PET-CT (CT2) images. This study aimed to investigate the feasibility of using deformable image registration (DIR) techniques to quantify radiation-induced metabolic changes on PET images. Five patients with non-small-cell lung cancer (NSCLC) treated with adaptive radiotherapy were considered. PET-CTs were acquired two weeks before RT and 18 fractions after the start of RT. DIR was performed from CT1 to CT2 using B-Spline and diffeomorphic Demons algorithms. The resultant displacements in the tumor region were then corrected using a hybrid finite element method (FEM). Bitmap masks generated from gross tumor volumes (GTVs) in PET1 were deformed using the four different displacement vector fields (DVFs). The conservation of total lesion glycolysis (TLG) in GTVs was used as a criterion to evaluate the quality of these registrations. The deformed masks were united to form a large mask which was then partitioned into multiple layers from center to border. The averages of SUV changes over all the layers were 1.0 ± 1.3, 1.0 ± 1.2, 0.8 ± 1.3, 1.1 ± 1.5 for the B-Spline, B-Spline + FEM, Demons and Demons + FEM algorithms, respectively. TLG changes before and after mapping using B-Spline, Demons, hybrid-B-Spline, and hybrid-Demons registrations were 20.2%, 28.3%, 8.7%, and 2.2% on average, respectively. Compared to image intensity-based DIR algorithms, the hybrid FEM modeling technique is better in preserving TLG and could be useful for evaluation of tumor response for patients with regressing tumors.

Quantification of CT-assessed radiation-induced lung damage in lung cancer patients treated with or without chemotherapy and cetuximab.

BACKGROUND AND PURPOSE: Prediction models for radiation-induced lung damage (RILD) are still unsatisfactory, with clinical toxicity endpoints that are difficult to quantify objectively. We therefore evaluated RILD more objectively, quantitatively and on a continuous scale measuring the lung tissue density changes per voxel. MATERIAL AND METHODS: Patients treated with radiotherapy (RT) alone, sequential and concurrent chemo-RT with and without the addition of cetuximab were studied. Follow-up computed tomography (CT) scans were co-registered using deformable registration to baseline CT scans. CT density changes were correlated to the RT dose delivered in every part of the lungs. RESULTS: One hundred and seventeen lung cancer patients were included. Mean dose to tumor was 60 Gy (range 45-79.2 Gy). Dose response curves showed a linear increase in the dose region between 0 and 65 Gy having a slope (based on coefficients of the multilevel model) expressed as a lung density increase per dose of 0.86 (95% CI 0.73-0.99), 1.31 (95% CI 1.19-1.43), 1.39 (95% CI 1.28-1.50) and 2.07 (95% CI 1.93-2.21) for patients treated only with RT (N=19), sequential chemo-RT (N=30), concurrent chemo-RT (N=49), and concurrent chemo-RT with cetuximab (N=19), respectively. CONCLUSIONS: CT density changes allow quantitative assessment of lung damage after fractionated RT, giving complementary information to standard used clinical endpoints. Patients receiving cetuximab showed a significantly larger dose response compared with other treatments.

Hypoxia imaging with [¹8F]HX4 PET in NSCLC patients: defining optimal imaging parameters.

BACKGROUND AND PURPOSE: [(18)F]HX4 is a promising hypoxia PET-tracer. Uptake, spatio-temporal stability and optimal acquisition parameters for [(18)F]HX4 PET imaging were evaluated in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: [(18)F]HX4 PET/CT images of 15 NSCLC patients were acquired 2h and 4h after injection (p.i.). Maximum standardized-uptake-value (SUV(max)), tumor-to-blood-ratio (TBR(max)), hypoxic fraction (HF) and contrast-to-noise-ratio (CNR) were determined for all lesions. To evaluate spatio-temporal stability, DICE-similarity and Pearson correlation coefficients were calculated. Optimal acquisition-duration was assessed by comparing 30, 20, 10 and 5 min acquisitions. RESULTS: Considerable uptake (TBR >1.4) was observed in 18/25 target lesions. TBR(max) increased significantly from 2 h (1.6 ± 0.3) to 4 h p.i. (2.0 ± 0.6). Uptake patterns at 2 h and 4 h p.i. showed a strong correlation (R=0.77 ± 0.10) with a DICE similarity coefficient of 0.69 ± 0.08 for the 30% highest uptake volume. Reducing acquisition-time resulted in significant changes in SUV(max) and CNR. TBR(max) and HF were only affected for scan-times of 5 min. CONCLUSIONS: The majority of NSCLC lesions showed considerable [(18)F]HX4 uptake. The heterogeneous uptake pattern was stable between 2 h and 4 h p.i. [(18)F]HX4 PET imaging at 4 h p.i. is superior to 2 h p.i. to reach highest contrast. Acquisition time may be reduced to 10 min without significant effects on TBR(max) and HF.

Quantification of radiation-induced lung damage with CT scans: the possible benefit for radiogenomics.

BACKGROUND: Radiation-induced lung damage (RILD) is an important problem. Although physical parameters such as the mean lung dose are used in clinical practice, they are not suited for individualised radiotherapy. Objective, quantitative measurements of RILD on a continuous instead of on an ordinal, semi-quantitative, semi-subjective scale, are needed. METHODS: Hounsfield unit (HU) changes before versus three months post-radiotherapy were correlated per voxel with the radiotherapy dose in 95 lung cancer patients. Deformable registration was used to register pre- and post-CT scans and the density increase was quantified for various dose bins. The dose-response curve for increased HU was quantified using the slope of a linear regression (HU/Gy). The end-point for the toxicity analysis was dyspnoea ≥ grade 2. RESULTS: Radiation dose was linearly correlated with the change in HU (mean R(2) = 0.74 ± 0.28). No differences in HU/Gy between groups treated with stereotactic radiotherapy, conventional radiotherapy alone, sequential or concurrent chemo- radiotherapy were observed. In the whole patient group, 33/95 (34.7%) had dyspnoea ≥ G2. Of the 48 patients with a HU/Gy below the median, 16 (33.3%) developed dyspnoea ≥ G2, while in the 47 patients with a HU/Gy above the median, 17 (36.1%) had dyspnoea ≥ G2 (not significant). Individual patients showed a nearly 21-fold difference in radiosensitivity, with HU/Gy ranging from 0 to 10 HU/Gy. CONCLUSIONS: HU changes identify objectively the whole range of individual radiosensitivity on a continuous, quantitative scale. CT density changes may allow more robust and accurate radiogenomics studies.