Signal-to-background Ratio Research Articles

Fully-Differential TPoS Resonators Based on Dual Interdigital Electrodes for Feedthrough Suppression

As one of the core components of MEMS (i.e., micro-electro-mechanical systems), thin-film piezoelectric-on-silicon (TPoS) resonators experienced a blooming development in the past decades due to unique features such as a remarkable capability of integration for attractive applications of system-on-chip integrated timing references. However, the parasitic capacitive feedthrough poses a great challenge to electrical detection of resonance in a microscale silicon-based mechanical resonator. Herein, a fully-differential configuration of a TPoS MEMS resonator based on a novel structural design of dual interdigital electrodes is proposed to eliminate the negative effect of feedthrough. The fundamental principle of feedthrough suppression was comprehensively investigated by using FEA (i.e., finite-element analysis) modeling and electrical measurements of fabricated devices. It was shown that with the help of fully-differential configuration, the key parameter of SBR (i.e., signal-to-background ratio) was significantly enhanced by greatly suppressing the in-phase signal. The S-parameter measurement results further verified the effectiveness of this novel feedthrough suppression strategy, and the insertion loss and SBR of proposed TPoS resonators were improved to 4.27 dB and 42.47 dB, respectively.

The impact of iterative reconstruction protocol, signal-to-background ratio and background activity on measurement of PET spatial resolution

The present study aims to assess the impact of acquisition time, different iterative reconstruction protocols as well as image context (including contrast levels and background activities) on the measured spatial resolution in PET images. Discovery 690 PET/CT scanner was used to quantify spatial resolutions in terms of full width half maximum (FWHM) as derived (i) directly from capillary tubes embedded in air and (ii) indirectly from 10mm-diameter sphere of the NEMA phantom. Different signal-to-background ratios (SBRs), background activity levels and acquisition times were applied. The emission data were reconstructed using iterative reconstruction protocols. Various combinations of iterations and subsets (it × sub) were evaluated. For capillary tubes, improved FWHM values were obtained for higher it × sub, with improved performance for PSF algorithms relative to non-PSF algorithms. For the NEMA phantom, by increasing acquisition times from 1 to 5min, intrinsic FWHM for reconstructions with it × sub 32 (54) was improved by 15.3% (13.2%), 15.1% (13.8%), 14.5% (12.8%) and 13.7% (12.7%) for OSEM, OSEM + PSF, OSEM + TOF and OSEM + PSF + TOF, respectively. Furthermore, for all reconstruction protocols, the FWHM improved with more impact for higher it × sub. Our results indicate that PET spatial resolution is greatly affected by SBR, background activity and the choice of the reconstruction protocols.

NIR-II fluorescence microscopic imaging of cortical vasculature in non-human primates.

Vasculature architecture of the brain can provide revealing information about mental and neurological function and disease. Fluorescence imaging in the second near-infrared (NIR-II) regime with less light scattering is a more promising method for detecting cortical vessels than traditional visible and NIR-I modes.Methods: Clinically approved dye indocyanine green (ICG) was used for NIR-II fluorescence imaging. Here, for the first time, we developed two NIR-II fluorescence microscopy systems for brain vasculature imaging in macaque monkeys. The first is a wide-field microscope with high temporal resolution for measuring blood flow velocity and cardiac impulse period, while the second is a high spatial resolution confocal microscope producing three-dimensional maps of the cortical microvascular network. Both were designed with flexibility to image various cortical locations on the head.Results: Here, ICG was proved to have high brightness in NIR-II region and an 8-fold QY increase in serum than in water. We achieved cerebrovascular functional imaging of monkey with high temporal resolution (25 frames/second) with wide-field microscope. The blood flow velocity of capillaries can be precisely calculated and the cardiac impulse period can be monitored as well. In vivo structural imaging of cerebrovasculature was accomplished with both high spatial lateral resolution (~8 µm) and high signal to background ratio (SBR). Vivid 3D reconstructed NIR-II fluorescence confocal microscopic images up to depth of 470 μm were also realized.Conclusion: This work comprises an important advance towards studies of neurovascular coupling, stroke, and other diseases relevant to neurovascular health in humans.

Deep UV Laser-Induced Fluorescence for Pharmaceutical Cleaning Validation.

Cleaning verification and validation is a requirement in the pharmaceutical industry. Due to the limited number of mobile devices that do effective and accurate onsite cleaning verification, it is mostly done via lab-based quality control techniques. These techniques, such as high-performance liquid chromatography (HPLC) or total organic carbon, often lead to extending the validation of cleaning by days. The void of more sensitive, accurate, and portable instruments to verify cleaning onsite has to be filled. The article discusses the use of deep ultra violet (DUV) laser-induced fluorescence for detecting carryover of active pharmaceutical ingredients (APIs) and detergents onsite. A modified spectrometer was used as an offsite bench type prototype for analyzing trace samples of API and cleaning detergents with various substrates. Even if the API to be detected has a low fluorescence efficiency, the specificity of the technique allows API traces having concentrations as low as ≈0.20 μg/cm2 to be identified. The work also shows the possibility of using a probe for validating cleaning of hard to reach areas using DUV laser-induced fluorescence. DUV laser-induced fluorescence of trace API over any polymer/glass substrate has better signal to background ratio (SBR) compared to FTIR absorption techniques. Processing times of DUV laser-induced fluorescence trace detection are shown to be much less than swab based methods.

A hybrid region growing tumour segmentation method for low contrast and high noise Nuclear Medicine (NM) images by combining a novel non-linear diffusion filter and global gradient measure (HNDF-GGM-RG)

Poor spatial resolution and low signal-to-noise ratio (SNR) along with the finite image sampling constraint make lesion segmentation on Nuclear Medicine (NM) images (e.g., PET–Positron Emission Tomography) a challenging task. Since the size, signal-to-background ratio (SBR) and SNR of lesion vary within and between patients, performance of the conventional segmentation methods are not consistent against statistical fluctuations. To overcome these limitations, a hybrid region growing segmentation method is proposed combining non-linear diffusion filter and global gradient measure (HNDF-GGM-RG). The performance of the algorithm is validated on PET images and compared with the 40%-fixed threshold and a state-of-the-art active contour (AC) methods. Segmented volume, dice similarity coefficient (DSC) and percentage classification error (% CE) were used as the quantitative figures of merit (FOM) using the torso NEMA phantom that contains six different sizes of spheres. A 2:1 SBR was created between the spheres and background and the phantom was scanned with a Siemens TrueV PET-CT scanner. 40T method is SNR dependent and overestimates the volumes (≈4.5 times). AC volumes match with the true volumes only for the largest three spheres. On the other hand, the proposed HNDF-GGM-RG volumes match closely with the true volumes irrespective of the size and SNR. Average DSC of 0.32 and 0.66 and % CE of 700% and 160% were achieved by the 40T and AC methods respectively. Conversely, average DSC and %CE are 0.70 and 60% for HNDF-GGM-RG and less dependent on SNR. Since two-sample t-test indicates that the performance of AC and HNDF-GGM-RG are statistically significant for the smallest three spheres and similar for the rest, HNDF-GGM-RG can be applied where the size, SBR and SNR are subject to change either due to alterations in the radiotracer uptake because of treatment or uptake variability of different radiotracers because of differences in their molecular pathways.

Naked-Eye Readout of Analyte-Induced NIR Fluorescence Responses by an Initiation-Input-Transduction Nanoplatform.

Fluorescence visualization (FV) in the near-infrared (NIR) window promises to break through the signal-to-background ratio (SBR) bottleneck of traditional visible-light-driven FV methods. However, straightforward NIR-FV has not been realized, owing to the lack of methods to readily transduce NIR responses into instrument-free, naked eye-recognizable outputs. Now, an initiation-input-transduction platform comprising a well-designed NIR fluorophore as the signal initiator and lanthanide-doped nanocrystals as the transducer for facile NIR-FV is presented. The analyte-induced off-on NIR signal serves as a sensitizing switch of transducer visible luminescence for naked-eye readout. The design is demonstrated for portable, quantitative detection of phosgene with significantly improved SBR and sensitivity. By further exploration of initiators, this strategy holds promise to create advanced NIR-FV probes for broad sensing applications.

Naked‐Eye Readout of Analyte‐Induced NIR Fluorescence Responses by an Initiation–Input–Transduction Nanoplatform

AbstractFluorescence visualization (FV) in the near‐infrared (NIR) window promises to break through the signal‐to‐background ratio (SBR) bottleneck of traditional visible‐light‐driven FV methods. However, straightforward NIR‐FV has not been realized, owing to the lack of methods to readily transduce NIR responses into instrument‐free, naked eye‐recognizable outputs. Now, an initiation–input–transduction platform comprising a well‐designed NIR fluorophore as the signal initiator and lanthanide‐doped nanocrystals as the transducer for facile NIR‐FV is presented. The analyte‐induced off–on NIR signal serves as a sensitizing switch of transducer visible luminescence for naked‐eye readout. The design is demonstrated for portable, quantitative detection of phosgene with significantly improved SBR and sensitivity. By further exploration of initiators, this strategy holds promise to create advanced NIR‐FV probes for broad sensing applications.

Joint compensation of motion and partial volume effects by iterative deconvolution incorporating wavelet-based denoising in oncologic PET/CT imaging

ObjectivesWe aim to develop and rigorously evaluate an image-based deconvolution method to jointly compensate respiratory motion and partial volume effects (PVEs) for quantitative oncologic PET imaging, including studying the impact of various reconstruction algorithms on quantification performance. ProceduresAn image-based deconvolution method that incorporated wavelet-based denoising within the Lucy-Richardson algorithm was implemented and assessed. The method was evaluated using phantom studies with signal-to-background ratios (SBR) of 4 and 8, and clinical data of 10 patients with 42 lung lesions ≤30 mm in diameter. In each study, PET images were reconstructed using four different algorithms: OSEM-basic, PSF, TOF, and TOFPSF. The performance was quantified using contrast recovery (CR), coefficient of variation (COV) and contrast-to-noise-ratio (CNR) metrics. Further, in each study, variabilities arising due to the four different reconstruction algorithms were assessed. ResultsIn phantom studies, incorporation of wavelet-based denoising improved COV in all cases. Processing images using proposed method yielded significantly higher CR and CNR particularly in small spheres, for all reconstruction algorithms and all SBRs (P < 0.05). In patient studies, processing images using the proposed method yielded significantly higher CR and CNR (P < 0.05). The choice of the reconstruction algorithm impacted quantification performance for changes in motion amplitude, tumor size and SBRs. ConclusionsOur results provide strong evidence that the proposed joint-compensation method can yield improved PET quantification. The choice of the reconstruction algorithm led to changes in quantitative accuracy, emphasizing the need to carefully select the right combination of reconstruction-image-based compensation methods.

Self-Illuminating Agents for Deep-Tissue Optical Imaging.

Optical imaging plays an indispensable role in biology and medicine attributing to its noninvasiveness, high spatiotemporal resolution, and high sensitivity. However, as a conventional optical imaging modality, fluorescence imaging confronts issues of shallow imaging depth due to the need for real-time light excitation which produces tissue autofluorescence. By contrast, self-luminescence imaging eliminates the concurrent light excitation, permitting deeper imaging depth and higher signal-to-background ratio (SBR), which has attracted growing attention. Herein, this review summarizes the progress on the development of near-infrared (NIR) emitting self-luminescence agents in deep-tissue optical imaging with highlighting the design principles including molecular- and nano-engineering approaches. Finally, it discusses current challenges and guidelines to develop more effective self-illuminating agents for biomedical diagnosis and treatment.

Improving the spectral qualities of major elements in soil by controlling the ambient pressure in time-resolved laser-induced breakdown spectroscopy.

Laser-induced breakdown spectroscopy (LIBS) is a powerful tool in the soil monitoring field, but the poor spectral quality limits its application. To improve the spectral quality of major elements in soil samples, a method based on controlling the ambient pressure and time sequence was introduced. Spectral qualities that include signal-to-background ratio (SBR), spectral stability, and spectral profile were all studied in different ambient pressures and delay times. The results show that the SBRs of Na and K elements increased from 20 to about 300, when the air pressure and delay time were controlled. Meanwhile, the relative standard deviations were improved from more than 30% to less than 5% due to the release of the self-absorption effect. This work proved that the spectral qualities of LIBS can be improved a lot by controlling the ambient pressure in the field of detecting major elements in soil.

Signal-to-background ratio and lateral resolution in deep tissue imaging by optical coherence microscopy in the 1700 nm spectral band

We quantitatively investigated the image quality in deep tissue imaging with optical coherence microscopy (OCM) in the 1700 nm spectral band, in terms of the signal-to-background ratio (SBR) and lateral resolution. In this work, to demonstrate the benefits of using the 1700 nm spectral band for OCM imaging of brain samples, we compared the imaging quality of OCM en-face images obtained at the same position by using a hybrid 1300 nm/1700 nm spectral domain (SD) OCM system with shared sample and reference arms. By observing a reflective resolution test target through a 1.5 mm-thick tissue phantom, which had a similar scattering coefficient to brain cortex tissue, we confirmed that 1700 nm OCM achieved an SBR about 6-times higher than 1300 nm OCM, although the lateral resolution of the both OCMs was similarly degraded with the increase of the imaging depth. Finally, we also demonstrated high-contrast deep tissue imaging of a mouse brain at a depth up to 1.8 mm by using high-resolution 1700 nm SD-OCM.

Response surface methodology for optimizing LIBS testing parameters: A case to conduct the elemental contents analysis in soil

Optimization of testing parameters are the prerequisite for laser induced breakdown spectroscopy (LIBS) further data analysis, which can offer important reference value for the soil detection in the field. This work investigated the influence of the main testing parameters laser energy (LE), delay time (DT), and lens to sample distance (LTSD) of LIBS system. Based on the spectral characteristic of main elements in soils, the testing parameters of LIBS for soil detection were obtained and verified. The optimization analysis of three testing parameters LE (50–160 mJ), DT (0.5–4.5 μs), and LTSD (94–102 mm) were conducted by response surface methodology (RSM). Central composite design (CCD) in RSM was introduced to carry out experimental runs. The combined signal-background-ratio (SBR) of characteristic spectral lines from main elements (Si, Fe, Mg, Ca, Al, Na, K, etc.) in soil were defined as the objective function (named YSBR). The interaction influences among three independent variables (LE, DT, and LTSD) on soil plasma characteristics were explored and the optimized testing parameters of LIBS were summarized. Results revealed as follows: the factor LE showed a remarkable linear effect to YSBR, and factors DT and LTSD exhibited opposite results. The interactive items of three factors displayed a non-significant relationship. Meanwhile, the quadratic items of LE2, DT2 and LTSD2 offered significant surface relationships. Through the RSM analysis, the optimized testing parameters for LIBS soil detection were LE: 103.09 mJ; DT: 2.92 μs; LTSD: 97.69 mm; and a peak value YSBR of 198.60. After that, the LIBS data of 21 representative soil samples were collected under the optimized LIBS testing parameters. Partial least squares regression (PLSR) was introduced to predict the main elemental contents. Results indicated that PLSR models offered promising outputs for predicting the contents of Al, Ca, Fe, K, Mg, and Na in the sampled soil, which revealed that the testing parameters of LIBS optimized by RSM were available. This work provided a theoretical basis for the accurate LIBS data analysis and regarded as a technical support for the field soil LIBS testing parameters selection.

Влияния связующего вещества, используемого при прессовании зол для лазерного пробоотбора, на качество аналитических сигналов определяемых элементов

This work is devoted to determining the chemical composition of coal ashes. We used the optical emission spectrometry with inductively coupled plasma and laser sampling as a research method. The aim of the work is to determine the limits of detection (LoDs) and quantitative determination (LoQs) of elements in ashes using polyvinyl alcohol (PVA) and microcrystalline cellulose (MCC) as binders. In this work, analytical signals of Al, Ba, Be, Ca, Cr, Cu, Fe, K, La, Li, Mg, Mn, Na, Ni, P, Pb, S, Sc, Sr, Ti, Y, V, Zr, and Zn were analyzed in tablets obtained from the standard samples ZUK-1, ZUK-2, SG-1A, SG-3, SGD-2A, and SO-1, compacted using PVA and MCC, as well as from binding agents themselves. To obtain compact materials based on fly ash and geological materials, both binders are suitable if their chemical purity is enough for analysis. However, when using both MCC and PVA, some drawbacks were identified. The intensities of analytical lines of the elements were determined lower during the ablation of compact ashes with MCC than with PVA. The signal-background ratio is lower when using MCC as a binder material compared with compacts based on PVA. However, the highest grade PVA according to GOST 10779-78, used in the work, contains an admixture of sodium, about 0.06 w. %, which interferes with quantitative measurements if the sodium content in the sample is comparable to this value, which can be extremely rare in the analysis of fly ashes.

Surface-Enhanced Raman Spectroscopy Based on Plasmonic Slot Waveguides With Free-Space Oblique Illumination

We report a novel on-chip approach for surface-enhanced Raman spectroscopy (SERS) using a plasmonic slot waveguide. The Raman signal is excited via free-space excitation and is collected by the waveguide. A significant improvement of the signal-to-background-ratio (SBR), as compared to the case of back-scattered Raman spectroscopy with waveguide-mode excitation, is demonstrated using a silicon nitride plasmonic slot waveguide with a 7-mm access waveguide. The flexible adjustment of the incident angle in free space and modification of waveguide geometry enables the further optimization of the pump-to-Stokes conversion efficiency. The combination of high SBR and long access waveguide allows the integration with additional photonics devices (sources, filters, spectrometers) on the same chip.

Excretable Lanthanide Nanoparticle for Biomedical Imaging and Surgical Navigation in the Second Near-Infrared Window.

Recently, various second near‐infrared window (NIR‐II, 1000–1700 nm) fluorophores have been synthesized for in vivo imaging with nonradiation, high resolution, and low autofluorescence. However, most of the NIR‐II fluorophores, especially inorganic nanoprobes, are mainly retained in the reticuloendothelial system (RES) such as the liver and spleen, leading to long‐term safety concerns. Herein, a type of lanthanide‐based excretable NIR‐II nanoparticle, RENPs@Lips, which can be quickly cleared out of body after intravenous administration with half‐lives of 23.0 h for the liver and 14.9 h for the spleen, is reported. Interestingly, over 90% of RENPs@Lips can be excreted through a hepatobiliary system within 72 h postinjection. The moderate blood half‐time (T 1/2 = 17.96 min) allows for multifunctional applications in delineating the hemodynamics of vascular disorders (artery thrombosis, ischemia, and tumor angiogenesis) and monitoring blood perfusion in response to acute ischemia. In addition, RENPs@Lips exhibit high performance in identifying orthotopic tumor vessels intraoperatively and embolization surgery under NIR‐II imaging navigation. Moreover, excellent signal‐to‐background ratio (SBR) is successfully achieved to facilitate sentinel lymph nodes biopsy (SLNB) with tumor‐bearing mice. The high biocompatibility, favorable excretability, and outstanding optical properties warrant RENPs@Lips as novel promising NIR‐II nanoparticles for future applications and translation into an interdisciplinary amalgamation of research in diverse fields.

NIR-II-Excited Intravital Two-Photon Microscopy Distinguishes Deep Cerebral and Tumor Vasculatures with an Ultrabright NIR-I AIE Luminogen.

Intravital fluorescence imaging of vasculature morphology and dynamics in the brain and in tumors with large penetration depth and high signal-to-background ratio (SBR) is highly desirable for the study and theranostics of vascular-related diseases and cancers. Herein, a highly bright fluorophore (BTPETQ) with long-wavelength absorption and aggregation-induced near-infrared (NIR) emission (maximum at ≈700 nm) is designed for intravital two-photon fluorescence (2PF) imaging of a mouse brain and tumor vasculatures under NIR-II light (1200 nm) excitation. BTPETQ dots fabricated via nanoprecipitation show uniform size of around 42 nm and a high quantum yield of 19 ± 1% in aqueous media. The 2PF imaging of the mouse brain vasculatures labeled by BTPETQ dots reveals a 3D blood vessel network with an ultradeep depth of 924 µm. In addition, BTPETQ dots show enhanced 2PF in tumor vasculatures due to their unique leaky structures, which facilitates the differentiation of normal blood vessels from tumor vessels with high SBR in deep tumor tissues. Moreover, the extravasation and accumulation of BTPETQ dots in deep tumor (more than 900 µm) is visualized under NIR-II excitation. This study highlights the importance of developing NIR-II light excitable efficient NIR fluorophores for in vivo deep tissue and high contrast tumor imaging.

Handheld motion stabilized laser speckle imaging.

Laser speckle imaging (LSI) is a wide-field, noninvasive optical technique that allows researchers and clinicians to quantify blood flow in a variety of applications. However, traditional LSI devices are cart or tripod based mounted systems that are bulky and potentially difficult to maneuver in a clinical setting. We previously showed that the use of a handheld LSI device with the use of a fiducial marker (FM) to account for motion artifact is a viable alternative to mounted systems. Here we incorporated a handheld gimbal stabilizer (HGS) to produce a motion stabilized LSI (msLSI) device to further improve the quality of data acquired in handheld configurations. We evaluated the msLSI device in vitro using flow phantom experiments and in vivo using a dorsal window chamber model. For in vitro experiments, we quantified the speckle contrast of the FM (KFM) using the mounted data set and tested 80% and 85% of KFM as thresholds for useable images (KFM,Mounted,80% and KFM,Mounted,85%). Handheld data sets using the msLSI device (stabilized handheld) and handheld data sets without the HGS (handheld) were collected. Using KFM,Mounted,80% and KFM,Mounted,85% as the threshold, the number of images above the threshold for stabilized handheld (38 ± 7 and 10 ± 2) was significantly greater (p = 0.031) than for handheld operation (16 ± 2 and 4 ± 1). We quantified a region of interest within the flow region (KFLOW), which led to a percent difference of 8.5% ± 2.9% and 7.8% ± 3.1% between stabilized handheld and handheld configurations at each threshold. For in vivo experiments, we quantified the speckle contrast of the window chamber (KWC) using the mounted data set and tested 80% of KWC (KWC,Mounted,80%). Stabilized handheld operation provided 53 ± 24 images above KWC,Mounted,80%, while handheld operation provided only 23 ± 13 images. We quantified the speckle flow index (SFI) of the vessels and the background to calculate a signal-to-background ratio (SBR) of the window chamber. Stabilized handheld operation provided a greater SBR (2.32 ± 0.29) compared to handheld operation (1.83 ± 0.21). Both the number of images above threshold and SBR were statistically significantly greater in the stabilized handheld data sets (p = 0.0312). These results display the improved usability of handheld data acquired with an msLSI device.

Development and validation of an alternative parameter for quantification of signals emitted by fluorescently labelled bacteria in microscopic images

In this study, an alternative parameter for quantifying the signals of fluorescently labelled bacteria (e.g. propidium iodide, Cyanine 3, etc.) in microscopic images was investigated. Three common parameters (mean grey value (MGV), mean grey value which is corrected for the background (MGVcwB) and the signal to background ratio (SBR) per bacterial cell) are used as reference parameters. As an alternative, the coefficient of variation (CV) is defined as the ratio of the logarithm of the standard deviation and the logarithm of the mean grey value of a bacterial cell in a microscopic image. The actual fluorescence value was safeguarded by measuring commercially available fluorescence latex microspheres at regular time intervals within our study. The precision and the correlation of the respective values of MGV, MGVcwB, SBR and CV taken from identical images were measured and subsequently normalized in order to enhance the inter-parameter comparability. The average precision of CV was the highest (89% ± 14) with decreasing numbers for MGVcwB, SBR, and MGV (78% ± 25, 71% ± 32, and, 52% ± 22, respectively). Changes in operational parameters, e.g., microscope settings, protocol steps, etc., yielded good results for the CV but less precise results for MGV, MGVcwB, and SBR in the analyses of identical images.In conclusion, using the alternative parameter CV, changes in the composition of microbial ecosystems may thus be investigated at the highest precision level.

Renal-clearable Molecular Semiconductor for Second Near-Infrared Fluorescence Imaging of Kidney Dysfunction.

Real-time imaging of kidney function is important to assess the nephrotoxicity of drugs and monitor the progression of renal diseases; however, it remains challenging because of the lack of optical agents with high renal clearance and high signal-to-background ratio (SBR). Herein, a second near-infrared (NIR-II) fluorescent molecular semiconductor (CDIR2) is synthesized for real-time imaging of kidney dysfunction in living mice. CDIR2 not only has a high renal clearance efficiency (≈90 % injection dosage at 24 h post-injection), but also solely undergoes glomerular filtration into urine without being reabsorbed and secreted in renal tubules. Such a unidirectional renal clearance pathway of CDIR2 permits real-time monitoring of kidney dysfunction in living mice upon nephrotoxic exposure. Thus, this study not only introduces a molecular renal probe but also provides useful molecular guidelines to increase the renal clearance efficiency of NIR-II fluorescent agents.

Near-infrared intraoperative molecular imaging with conventional neurosurgical microscope can be improved with narrow band "boost" excitation.

Intraoperative visualization of brain tumors with near-infrared (NIR)-fluorescent dyes is an emerging method for tumor margin approximation but are limited by existing fluorescence detection platforms. We previously showed that a dedicated NIR imaging platform outperformed a state-of-the-art neurosurgical microscope in fluorescence signal characteristics. This study examined whether conventional neurosurgical microscope NIR signal could be improved with the addition of a narrow wavelength excitation source. Imaging was conducted with a broad-spectrum neurosurgical microscope and commercial near-infrared module. Addition of an 805-nm laser was used to "boost" NIR excitation of indocyanine green (ICG). In vitro quantification was performed on serial dilutions of ICG. Patients underwent tumor resection with delayed 24-h imaging of ICG infusion. NIR fluorescence of dura, cortex, or tumor was quantified from images prior to (pre-boost) and following added excitation with the laser (post-boost). Signal to background ratio (SBR) of pre- and post-boost was calculated as a readout of image enhancement. In vitro, excitation boost effected a 29% increase in mean SBR in six serial dilutions of ICG. Intraoperative boost was performed in 11 patients including meningioma, glioblastoma multiforme, and metastases. Increase in tumor fluorescence was pronounced under direct tumor visualization. Across all patients, boost excitation resulted in 35% mean improvement from pre-boost SBR (p < 0.001). Neurosurgical microscopes remain the preferred method of visualizing tumor during intracranial surgery. However, current modalities for NIR signal detection are suboptimal. We demonstrate that augmentation of a fluorescence microscope module with a focused excitation source is a simple mechanism of improving NIR tumor visualization. NCT03262636.