Parathyroid gland blood supply disruption causes post-surgical complications in nearly half of thyroid surgeries. Assessment of parathyroid gland vascularity is thus critical to preserving parathyroid function. The previous study used laser speckle contrast imaging (LSCI) for parathyroid vascularity difference detection and showed reliability and promises that the LSCI device can provide during surgery. The current study takes a step forward and developed a handheld laser speckle contrast imaging device that had shown the ability to detect flow and distinguish vascular of parathyroids in vivo.
Near infrared autofluorescence (NIRAF) can aid in identifying parathyroid glands (PGs) during thyroidectomies. Additionally, surgeons use indocyanine green (ICG) to evaluate PG perfusion. However, there is spectral overlap between PGs and ICG making parathyroid identification challenging after ICG injection. ICG dose adjustment may be needed for quantitative tissue perfusion assessment without interfering with PG NIRAF detection. This work investigated the utility of probe-based detection to determine PG vascularity using ICG doses of 0.25 and 1.25 mg. A mathematical model was also developed to determine the ICG dosage threshold for concurrent vascularity assessment and NIRAF detection of PGs.
Surgeons find it challenging to preserve healthy parathyroid glands (PGs) and confirm removal of diseased PGs during parathyroidectomies, often leading to postoperative complications and costly frozen section analysis (FSA). PTeye™ - a fiber-optic probe-based system that detects near infrared autofluorescence (NIRAF) was FDA-cleared to serve as an intraoperative adjunct device to aid in intraoperative PG identification. We sought to assess the impact of NIRAF detection during parathyroidectomies for the first time through a single-center randomized clinical trial. Our current findings indicate that PTeye™ could improve a surgeon’s confidence in PG identification, while potentially reducing FSAs needed during parathyroidectomies.
Several studies have already demonstrated that near infrared autofluorescence (NIRAF) detection can be reliably used to detect parathyroid glands (PGs) in adults. However, its scope remains unexplored in the pediatric population, who are more prone to accidental PG damage during neck surgeries. Our preliminary findings obtained from pediatric patients who underwent thyroidectomies, indicate a PG detection rate of 94.4% using NIRAF detection with a fiber-optic probe-based approach. Due to the complexities associated with surgeries performed through tiny neck incisions in the pediatric population, the fiber-optic probe-based NIRAF detection can be valuable for real-time label-free PG identification during pediatric neck surgeries.
Oropharyngeal squamous cell carcinoma (OPSCC) which refers to the cancer of the back of the throat, including the base of tongue and tonsils, has rapidly increased the past several decades and if undiagnosed, the tumors metastasize leading to many complications and decreased survival. In this study, Raman spectroscopy (RS) in combination with data classification algorithms was used to examine tonsil specimens (normal, benign, and malignant) to determine if RS could serve as a viable tool for real-time sensitive detection of OPSCC and ultimately other HPV-linked cancers.
Combined fingerprint and high wavenumber spatially offset Raman spectroscopy was implemented for depth-dependent biochemical characterization. Quantitative spectral analysis of water and other components was conducted in layered optical phantoms.
Hypoparathyroidism is a major complication after thyroid surgery, due to damage to healthy parathyroid glands. Near infrared autofluorescence imaging and laser speckle contrast imaging have been shown to address the two causes of parathyroid function loss – accidental removal, and damage to the parathyroid blood supply respectively. Here, we present an instrument that combines both techniques to enable intraoperative parathyroid identification and viability assessment in real-time and without the need for contrast agents. The performance of the device was evaluated intraoperatively in patients undergoing thyroidectomy and parathyroidectomy.
Identifying parathyroid glands can be challenging for surgeons during head and neck operations. For the surgeon, it becomes essential to preserve healthy parathyroid glands, while successfully removing diseased parathyroid glands. This study presents PTeye – a commercial fiber probe-based device that was designed for intraoperative parathyroid identification by detecting near infrared autofluorescence. The results of this study demonstrate that PTeye had 95% accuracy in identifying parathyroid glands in 78 patients. The device had an overall detection rate of 97% for healthy and diseased parathyroid glands. PTeye could also quantify parathyroid vascularity in real-time by using indocyanine green during neck surgeries.
KEYWORDS: Tumors, Breast cancer, Mammography, Phototherapy, 3D modeling, Tumor growth modeling, Cancer, Resistance, 3D image processing, Electron transport
Innate differences among breast cancer phenotypes are often studied from the perspective of single protein expressions or by fluorescent imaging using molecular tags. While these techniques can offer useful insights into breast cancer taxonomy, they do not easily translate to clinical care. Nonlinear optical microscopy has revolutionized our ability to study biochemical processes, as it offers a label-free approach to study differences in cancer phenotypes that may provide insight into factors affecting prognosis and treatment strategies. The endogenous chemical specificity offered by nonlinear imaging modalities like Stimulated Raman Scattering (SRS) and Multiphoton Fluorescence (MPF) are attractive alternatives to fluorescent imaging to study intracellular biochemistry. Here we utilize a multimodal imaging platform to characterize lipogenesis in HER2+ cell lines through SRS and metabolic activity by MPF of NADH/FAD to investigate unique signals related to HER2 status.
The process of translating lab-built innovations into viable tools for clinical applications is complex and costly. Clearing the regulatory processes is the pivotal step that eventually enables these devices to be implemented for the intended clinical applications. Unfortunately this task could be challenging and time-consuming for unprepared academics aiming to translate their inventions/discoveries from bench to bedside. Therefore there is a vital need to educate researchers on adopting the best approach when dealing with regulatory submissions to ensure smoother translation of their respective technologies.
To understand the bench to bedside pathway more clearly, we will utilize the example of the first-ever discovery of near infrared autofluorescence in parathyroid glands at Vanderbilt University. Subsequently a lab-built system was designed for label-free intraoperative parathyroid identification during thyroid and parathyroid surgeries, which was tested across 162 patients with high accuracy. Subsequently Vanderbilt University partnered with AiBiomed (Santa Barbara, California) to develop a clinical prototype called ‘PTeye’ that was user-friendly for surgeons and ready-to-use in operation rooms. The ‘PTeye’ was then evaluated across 81 patients in a single-blinded, multi-centric study that yielded 96% accuracy. Relying on this data, Vanderbilt University and AiBiomed initiated the ‘de novo’ application process with the Food and Drug Administration (FDA) for regulatory clearance of the ‘PTeye’. The ‘de novo’ approach was selected since the instrument design and intended use of ‘PTeye’ did not resemble that of any pre-existing medical devices. Following a successful review, the FDA eventually granted permission to market ‘PTeye’ as an adjunct intraoperative tool for label-free parathyroid identification.
As much as 50% of thyroid procedures result in post-surgical hypoparathyroidism and consequent hypocalcemia. This can be due to accidental removal of the parathyroid glands or damage to their blood supply that renders them non-viable. The parathyroids are the body’s main organs for regulating calcium, so loss of their function will require lifelong medication to maintain normal calcium levels. Work has been done separately to address both causes of parathyroid function loss. Autofluorescence spectroscopy/imaging has been shown to be highly accurate in distinguishing parathyroid glands from other tissues in the neck, helping avoid accidental removal of parathyroid glands. Laser speckle contrast imaging (LSCI) is capable of accurately identifying parathyroid glands that have suffered vascular compromise, providing guidance on whether to transplant a parathyroid. Here, we present an instrument that combines both techniques to enable parathyroid identification and viability assessment. Additionally, we developed algorithms to automate the extraction of parathyroid viability information from speckle contrast images using information from fluorescence images. This makes the device more autonomous and speeds up the process of providing information to the surgeon. Testing on ex vivo parathyroid and thyroid specimens revealed that the algorithm performs best when the ratio of parathyroid to thyroid fluorescence is at least 1.5. The device will also be tested on patients undergoing parathyroidectomy at Vanderbilt University Medical Center. Autofluorescence data will be validated by histology to confirm parathyroid tissue, and LSCI data will be validated by ligating the blood supply to the diseased parathyroid gland in preparation for removal.
Fluorescence imaging is a well-established optical modality that has been used to localize and track fluorophores in vivo and has demonstrated great potential for surgical guidance. Despite the variety of fluorophores currently being researched, many existing intraoperative fluorescence imaging systems are specifically designed for a limited number of applications. We present a modular wide-field fluorescence overlay tissue imaging system for intraoperative surgical guidance that is comprised of commercially available standardized components. Its modular layout allows for the accommodation of a broad range of fluorophores, fields of view (FOV), and spatial resolutions while maintaining an integrated portable design for intraoperative use. Measurements are automatic and feature a real-time projection overlay technique that intuitively displays fluorescence maps directly onto a 15 × 15 cm2 FOV from a working distance of 35 cm. At a 20-ms exposure time, 10 μM samples of indocyanine green could be measured with high signal-to-noise ratio and was later tested in an in vivo mouse model before finally being demonstrated for intraoperative autofluorescence imaging of human soft tissue sarcoma margins. The system’s modular design and ability to enable naked-eye visualization of wide-field fluorescence allow for the flexibility to adapt to numerous clinical applications and can potentially extend the adoption of fluorescence imaging for intraoperative use.
As many as 80,000 patients a year in the US undergo thyroidectomies or parathyroidectomies for diseased glands. About 21% of these surgeries result in disruption of blood supply to health parathyroid glands, which, if unaddressed, may result in long-term hypocalcemia. Surgeons need to know as soon as possible whether or not the blood supply to a parathyroid gland has been disrupted, as this informs their decision on whether or not to excise and reimplant the gland. There is a non-trivial failure rate involved in this transplantation process, and in the absence of an objective gold-standard surgeons often rely on subjective visual inspection in making this decision. Here we present Laser Speckle Imaging as a real-time objective method to assess parathyroid viability. Our device consists of a 785 nm laser source and a near-infrared camera with a zoom lens, positioned above the surgical field with an articulated arm. With the laser diffusing light onto the tissue, the camera acquires images which are processed in real-time and displayed on a monitor. These speckle contrast images are then averaged and the relative difference in speckle contrast between the parathyroid gland and surrounding thyroid tissue is calculated and correlated with the surgeon’s assessment of viability. Preliminary findings from in vivo measurement of 9 diseased glands show 100% agreement with the surgeon when taking a greater than 5% relative difference to indicate devascularization. This device has the potential to be used as an intraoperative tool for assessing parathyroid viability.
Nonlinear optical imaging modalities (multiphoton excited fluorescence, second and third harmonic generation) applied in vivo are increasingly promising for clinical diagnostics and the monitoring of cancer and other disorders, as they can probe tissue with high diffraction-limited resolution at near-infrared (IR) wavelengths. However, high peak intensity of femtosecond laser pulses required for two-photon processes causes formation of cyclobutane-pyrimidine-dimers (CPDs) in cellular deoxyribonucleic acid (DNA) similar to damage from exposure to solar ultraviolet (UV) light. Inaccurate repair of subsequent mutations increases the risk of carcinogenesis. In this study, we investigate CPD damage that results in Chinese hamster ovary cells in vitro from imaging them with two-photon excited autofluorescence. The CPD levels are quantified by immunofluorescent staining. We further evaluate the extent of CPD damage with respect to varied wavelength, pulse width at focal plane, and pixel dwell time as compared with more pronounced damage from UV sources. While CPD damage has been expected to result from three-photon absorption, our results reveal that CPDs are induced by competing two- and three-photon absorption processes, where the former accesses UVA absorption band. This finding is independently confirmed by nonlinear dependencies of damage on laser power, wavelength, and pulse width.
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