Performance of a novel spectroscopy-based tool for adjuvant therapy decision-making in hormone receptor-positive breast cancer: a validation study.

PURPOSE: Digistain Index (DI), measured using an inexpensive mid-infrared spectrometer, reflects the level of aneuploidy in unstained tissue sections and correlates with tumor grade. We investigated whether incorporating DI with other clinicopathological variables could predict outcomes in patients with early breast cancer. METHODS: DI was calculated in 801 patients with hormone receptor-positive, HER2-negative primary breast cancer and ≤ 3 positive lymph nodes. All patients were treated with systemic endocrine therapy and no chemotherapy. Multivariable proportional hazards modeling was used to incorporate DI with clinicopathological variables to generate the Digistain Prognostic Score (DPS). DPS was assessed for prediction of 5- and 10-year outcomes (recurrence, recurrence-free survival [RFS] and overall survival [OS]) using receiver operating characteristics and Cox proportional hazards regression models. Kaplan-Meier analysis evaluated the ability of DPS to stratify risk. RESULTS: DPS was consistently highly accurate and had negative predictive values for all three outcomes, ranging from 0.96 to 0.99 at 5 years and 0.84 to 0.95 at 10 years. DPS demonstrated statistically significant prognostic ability with significant hazard ratios (95% CI) for low- versus high-risk classification for RFS, recurrence and OS (1.80 [CI 1.31-2.48], 1.83 [1.32-2.52] and 1.77 [1.28-2.43], respectively; all P < 0.001). CONCLUSION: DPS showed high accuracy and predictive performance, was able to stratify patients into low or high-risk, and considering its cost and rapidity, has the potential to offer clinical utility.

Digistain: a digital staining instrument for histopathology.

We describe a new mid-infrared (mid-IR) imaging method specifically designed to augment the H + E tissue staining protocol. Images are taken with bespoke IR filters at wavelengths that enable chemical maps to be generated, corresponding to the cytoplasmic (amide) and nuclear (phosphodiester) components of unstained oesophageal tissue sections. A suitably calibrated combination of these generates false colour computer images that reproduce not only the tissue morphology, but also accurate and quantitative distributions of the nuclear-to-cytoplasmic ratio throughout the tissue section. This parameter is a well documented marker of malignancy, and because the images can be taken and interpreted by clinically trained personnel in a few seconds, we believe this new "digistain" approach makes spectroscopic mid-IR imaging techniques available for the first time as a practical, specific and sensitive augmentation to standard clinical cancer diagnosis methods.

Fano resonances in nanoscale plasmonic systems: a parameter-free modeling approach.

The interaction between plasmonic resonances, sharp modes, and light in nanoscale plasmonic systems often leads to Fano interference effects. This occurs because the plasmonic excitations are usually spectrally broad and the characteristic narrow asymmetric Fano line-shape results upon interaction with spectrally sharper modes. By considering the plasmonic resonance in the Fano model, as opposed to previous flat continuum approaches, here we show that a simple and exact expression for the line-shape can be found. This allows the role of the width and energy of the plasmonic resonance to be properly understood. As examples, we show how Fano resonances measured on an array of gold nanoantennas covered with PMMA, as well as the hybridization of dark with bright plasmons in nanocavities, are well reproduced with a simple exact formula and without any fitting parameters.

Comparison of a diode pumped Er:YSGG and Er:YAG laser in the bounce geometry at the 3 µm transition.

A comparative study is made of the laser crystals 50 at. % Er:YAG and 50 at. % Er:YSGG. Both lasers are constructed in the bounce geometry with quasi continuous wave (QCW) diode pumping. In Er:YAG, pulse energies of up to ~31mJ, slope efficiency of 12.6% and a red-shift in laser wavelength are observed with a final and dominant wavelength of 2.936µm. In Er:YSGG, higher performance is achieved with pulse energies of ~55mJ, slope efficiency of 20.5% and a single transition wavelength of 2.797µm observed. The study indicates that diode pumped Er:YSGG is a superior laser source at 3µm than Er:YAG and it has greater energy storage potential for Q-switched operation.

A benchtop, ultrafast infrared spectroscopic imaging system for biomedical applications.

We discuss the potential biomedical applications for a novel infrared spectroscopic microimaging system. A tunable, table top solid-state laser has been coupled to a commercial infrared microscope, fitted with a modified high resolution infrared camera, to create a unique tool for midinfrared imaging. The system is capable of performing broadband imaging at a diffraction-limited spatial resolution, as is demonstrated here by spatially resolved spectroscopy of polymer test samples with a spectral resolution of 20 cm(-1). The large pulse energies (tens of microjoules) offer previously unobtainable combinations of high signal-to-noise levels and rapid data collection times which are superior to current stand-alone laboratory instruments by many decades. Coupled with the short (100 ps) short pulse duration, these characteristics promise to make a wide range of time-resolved and reflection mode imaging experiments possible with live biological systems.