Accurate machine-specific reference and small-field dosimetry for a self-shielded neuro-radiosurgical system.

BACKGROUND: The newly available ZAP-X stereotactic radiosurgical system is designed for the treatment of intracranial lesions, with several unique features that include a self-shielding, gyroscopic gantry, wheel collimation, non-orthogonal kV imaging, short source-axis distance, and low-energy megavoltage beam. Systematic characterization of its radiation as well as other properties is imperative to ensure its safe and effective clinical application. PURPOSE: To accurately determine the radiation output of the ZAP-X with a special focus on the smaller diameter cones and an aim to provide useful recommendations on quantification of small field dosimetry. METHODS: Six different types of detectors were used to measure relative output factors at field sizes ranging from 4 to 25 mm, including the PTW microSilicon and microdiamond diodes, Exradin W2 plastic scintillator, Exradin A16 and A1SL ionization chambers, and the alanine dosimeter. The 25 mm cone served as the reference field size. Absolute dose was determined with both TG-51-based dosimetry using a calibrated PTW Semiflex ion chamber and measurements using alanine dosimeters. RESULTS: The average radiation output factors (maximum deviation from the average) measured with the microDiamond, microSilicon, and W2 detectors were: for the 4 mm cone, 0.741 (1.0%); for the 5 mm cone: 0.817 (1.0%); for the 7.5 mm cone: 0.908 (1.0%); for the 10 mm cone: 0.946 (0.4%); for the 12.5 mm cone: 0.964 (0.2%); for the 15 mm cone: 0.976 (0.1%); for the 20 mm cone: 0.990 (0.1%). For field sizes larger than 10 mm, the A1SL and A16 micro-chambers also yielded consistent output factors within 1.5% of those obtained using the microSilicon, microdiamond, and W2 detectors. The absolute dose measurement obtained with alanine was within 1.2%, consistent with combined uncertainties, compared to the PTW Semiflex chamber for the 25 mm reference cone. CONCLUSION: For field sizes less than 10 mm, the microSilicon diode, microDiamond detector, and W2 scintillator are suitable devices for accurate small field dosimetry of the ZAP-X system. For larger fields, the A1SL and A16 micro-chambers can also be used. Furthermore, alanine dosimetry can be an accurate verification of reference and absolute dose typically measured with ion chambers. Use of multiple suitable detectors and uncertainty analyses were recommended for reliable determination of small field radiation outputs.

Translational Potential of Fluorescence Polarization for Breast Cancer Cytopathology.

Breast cancer is the most common malignancy in women. The standard of care for diagnosis involves invasive core needle biopsy followed by time-consuming histopathological evaluation. A rapid, accurate, and minimally invasive method to diagnose breast cancer would be invaluable. Therefore, this clinical study investigated the fluorescence polarization (Fpol) of the cytological stain methylene blue (MB) for the quantitative detection of breast cancer in fine needle aspiration (FNA) specimens. Cancerous, benign, and normal cells were aspirated from excess breast tissues immediately following surgery. The cells were stained in aqueous MB solution (0.05 mg/mL) and imaged using multimodal confocal microscopy. The system provided MB Fpol and fluorescence emission images of the cells. Results from optical imaging were compared to clinical histopathology. In total, we imaged and analyzed 3808 cells from 44 breast FNAs. Fpol images displayed quantitative contrast between cancerous and noncancerous cells, whereas fluorescence emission images showed the morphological features comparable to cytology. Statistical analysis demonstrated that MB Fpol is significantly higher (p < 0.0001) in malignant vs. benign/normal cells. It also revealed a correlation between MB Fpol values and tumor grade. The results indicate that MB Fpol could provide a reliable, quantitative diagnostic marker for breast cancer at the cellular level.

Design and Validation of a Handheld Optical Polarization Imager for Preoperative Delineation of Basal Cell Carcinoma.

BACKGROUND: Accurate removal of basal cell carcinoma (BCC) is challenging due to the subtle contrast between cancerous and normal skin. A method aiding with preoperative delineation of BCC margins would be valuable. The aim of this study was to implement and clinically validate a novel handheld optical polarization imaging (OPI) device for rapid, noninvasive, in vivo assessment of skin cancer margins. METHODS: The handheld imager was designed, built, and tested. For clinical validation, 10 subjects with biopsy-confirmed BCC were imaged. Presumable cancer margins were marked by the study surgeon. The optical images were spectrally encoded to mitigate the impact of endogenous skin chromophores. The results of OPI and of the surgeon's preoperative visual assessment were compared to clinical intraoperative histopathology. RESULTS: As compared to the previous prototype, the handheld imager incorporates automated image processing and has 10-times shorter acquisition times. It is twice as light and provides twice as large a field of view. Clinical validation demonstrated that margin assessments using OPI were more accurate than visual assessment by the surgeon. The images were in good correlation with histology in 9 out of 10 cases. CONCLUSIONS: Handheld OPI could improve the outcomes of skin cancer treatments without impairing clinical workflows.

Fluorescence Polarization Imaging of Methylene Blue Facilitates Quantitative Detection of Thyroid Cancer in Single Cells.

BACKGROUND: Diagnostic accuracy of the standard of care fine-needle aspiration cytology (FNAC) remains a significant problem in thyroid oncology. Therefore, a robust and accurate method for reducing uncertainty of cytopathological evaluation would be invaluable. METHODS: In this double-blind study, we employed fluorescence emission and quantitative fluorescence polarization (Fpol) confocal imaging for sorting thyroid cells into benign/malignant categories. Samples were collected from malignant tumors, benign nodules, and normal thyroid epithelial tissues. RESULTS: A total of 32 samples, including 12 from cytologically indeterminate categories, were stained using aqueous methylene blue (MB) solution, imaged, and analyzed. Fluorescence emission images yielded diagnostically relevant information on cytomorphology. Significantly higher MB Fpol was measured in thyroid cancer as compared to benign and normal cells. The results obtained from 12 indeterminate samples revealed that MB Fpol accurately differentiated benign and malignant thyroid nodules. CONCLUSIONS: The developed imaging approach holds the potential to provide an accurate and objective biomarker for thyroid cancer, improve diagnostic accuracy of cytopathology, and decrease the number of lobectomy and near-total thyroidectomy procedures.

Temperature induced changes in the optical properties of skin in vivo.

Knowledge of temperature-induced changes of skin optical properties is required for accurate dosimetry of photothermal treatments. We determined and compared in vivo optical properties of mouse ear skin at different temperatures. The diffuse reflectance, total and diffuse transmittance were measured in the spectral range from 400 to 1650 nm using an integrating sphere spectrometer at the temperatures of 25 °C, 36 °C and 60 °C. Target temperatures were attained and maintained using an automated heater equipped with a sensor for feed-back and control. Temperature and temperature induced morphological changes of skin were monitored using an infrared thermal camera and reflectance confocal microscopy, respectively. An inverse Monte Carlo technique was utilized to determine absorption, scattering, and anisotropy factors from the measured quantities. Our results indicate significant differences between the optical properties of skin at different temperatures. Absorption and scattering coefficients increased, whereas anisotropy factors decreased with increasing temperature. Changes in absorption coefficients indicate deoxygenation of hemoglobin, and a blue shift of water absorption bands. Confocal imaging confirmed that our observations can be explained by temperature induced protein denaturation and blood coagulation. Monitoring spectral responses of treated tissue may become a valuable tool for accurate dosimetry of light treatments.

Dual-Wavelength Optical Polarization Imaging for Detecting Skin Cancer Margins.

Treatment of keratinocyte carcinomas requires an assessment of the extent of tumor spread. Visual delineation of tumor margins is error-prone owing to the limited contrast between cancerous and normal skin. In this contribution, we introduce spectrally-encoded optical polarization imaging and evaluate its performance for preoperative demarcation of keratinocyte carcinomas. Subjects with basal or squamous cell carcinoma, scheduled for Mohs surgery, were enrolled. The surgeon outlined the clinical boundary of each lesion preoperatively. Optical images of the lesions were then acquired at 440 and 640 nm. Spectral encoding of the experimental images minimized the impact of background pigmentation and vascularization. The surgeon was blinded to the imaging results. Margin assessments by imaging and by the surgeon were recorded and compared with the intraoperative histopathology. In total, 53 lesions were imaged in vivo. Thirteen cases required more than one Mohs stage. In all these cases, images accurately visualized the tumor. For cases negative following the first Mohs stage, margin assessments correlated with histopathology in 39 out of 40 cases. Imaging demonstrated 100% sensitivity and 98% specificity. Spectrally-encoded optical polarization imaging may prove valuable for real-time noninvasive preoperative delineation of skin cancer.

Multimodal quantitative imaging of brain cancer in cultured cells.

Fluorescence emission, polarization and subcellular localization of methylene blue (MB) were studied in four cancerous and two normal human brain cell lines. Fluorescence emission and polarization images were acquired and analyzed. The co-localization of MB with mitochondria, lysosomes and nuclei of the cells was evaluated. Glioblastoma cells exhibited significantly higher MB fluorescence polarization compared to normal astrocytes. Preferential accumulation of MB in mitochondria of glioblastoma cells may explain higher fluorescence polarization values in cancer cells as compared to normal. These findings may lead to the development of a quantitative method for the detection of brain cancer in single cells.

Collagen disruption as a marker for basal cell carcinoma in presurgical margin detection.

INTRODUCTION AND OBJECTIVE: Nonmelanoma skin cancers (NMSCs) are the most common malignancies in the United States. Surgery is the most common treatment for these tumors, but pre-operative identification of surgical margins is challenging. The objective in this study was to determine whether optical polarization imaging (OPI) could be used prior to surgery to detect the extent of subclinical tumor spread by monitoring disruption in collagen. MATERIALS AND METHODS: OPI is a non-invasive and rapid imaging modality that highlights the structure of dermal collagen. OPI was used preoperatively at wavelengths of 440 and 640 nm to perform imaging of NMSCs on six patients scheduled to undergo Mohs surgery for biopsy-proven basal cell carcinoma. This pilot study did not alter the course of routine MMS for any of the patients. The surgeon was blinded from the preoperative imaging results and completed the entire procedure without relying on the new technology. The study was conducted in an outpatient surgical setting. Patients over 18 years of age with biopsy-proven basal cell carcinoma participated. RESULTS AND CONCLUSION: OPI accurately predicted the presence or absence of tumor at the surgical margin in six out of six cases, as confirmed on histology. OPI may allow efficient surgical planning by identifying tumor extension beyond visibly involved skin. Lasers Surg. Med. 50:902-907, 2018. © 2018 Wiley Periodicals, Inc.