Project description:BACKGROUND:Near-infrared (NIR) tumor contrast is achieved through the "second-window ICG" technique, which relies on passive accumulation of high doses of indocyanine green (ICG) in neoplasms via the enhanced permeability and retention effect. OBJECTIVE:To report early results and potential challenges associated with the application of second-window ICG technique in endonasal endoscopic, ventral skull-base surgery, and to determine potential predictors of NIR signal-to-background ratio (SBR) using endoscopic techniques. METHODS:Pituitary adenoma (n = 8), craniopharyngioma (n = 3), and chordoma (n = 4) patients received systemic infusions of ICG (5 mg/kg) approximately 24 h before surgery. Dual-channel endoscopy with visible light and NIR overlay were photodocumented and analyzed post hoc. RESULTS:All tumors (adenoma, craniopharyngioma, chordoma) demonstrated NIR positivity and fluoresced with an average SBR of 3.9 ± 0.8, 4.1 ± 1.7, and 2.1 ± 0.6, respectively. Contrast-enhanced T1 signal intensity proved to be the single best predictor of observed SBR (P = .0003). For pituitary adenomas, the sensitivity, specificity, positive predictive value, and negative predictive value of NIR-guided identification of tumor was 100%, 20%, 71%, and 100%, respectively. CONCLUSION:In this preliminary study of a small set of patients, we demonstrate that second-window ICG can provide NIR optical tumor contrast in 3 types of ventral skull-base tumors. Chordomas demonstrated the weakest NIR signal, suggesting limited utility in those patients. Both nonfunctional and functional pituitary adenomas appear to accumulate ICG, but utility for margin detection for the adenomas is limited by low specificity. Craniopharyngiomas with third ventricular extension appear to be a particularly promising target given the clean brain parenchyma background and strong SBR.
Project description:BackgroundAlthough real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense.ObjectiveTo propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease.MethodsFifteen patients were identified and administered a Food and Drug Administration-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) before surgical resection. An NIR camera was utilized to localize the tumor before resection and to visualize surgical margins following resection. Neuropathology and magnetic resonance imaging data were used to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue.ResultsNIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low-grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12 of 15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with signal-to-background ratio (P = .03). Nonenhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71).ConclusionWith the use of Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity.Abbreviations5-ALA, 5-aminolevulinic acidEPR, enhanced permeability and retentionFDA, Food and Drug AdministrationGBM, glioblastomaICG, indocyanine greenNIR, near-infraredNPV, negative predictive valuePPV, positive predictive valueROC, receiver operating characteristicROI, region of interestSBR, signal-to-background ratioWHO, World Health Organization.
Project description:In vivo optical imaging with near-infrared (NIR) probes is an established method of diagnostics in preclinical and clinical studies. However, the specificities of these probes are difficult to validate ex vivo due to the lack of NIR flow cytometry. To address this limitation, we modified a flow cytometer to include an additional NIR channel using a 752 nm laser line. The flow cytometry system was tested using NIR microspheres and cell lines labeled with a combination of visible range and NIR fluorescent dyes. The approach was verified in vivo in mice evaluated for immune response in lungs after intratracheal delivery of the NIR contrast agent. Flow cytometry of cells obtained from the lung bronchoalveolar lavage demonstrated that the NIR dye was taken up by pulmonary macrophages as early as 4-h post-injection. This combination of optical imaging with NIR flow cytometry extends the capability of imaging and enables complementation of in vivo imaging with cell-specific studies.
Project description:Imaging agents with affinity for bone can enable early detection of changes to bone mineral density, which is a hallmark of many bone-associated pathologies such as Paget's disease and osteoporosis. Here, we report the development of a polymer nanoparticle (NP)-based multimodal imaging probe that enables visualization of bone mineral phase in near-infrared (NIR) optical tomography and detection in T2-weighted magnetic resonance imaging (MRI). Ultrasmall superparamagnetic iron oxide was first encapsulated in NPs derived by blending poly(dl-lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) with N-hydroxysuccinimide functionalized-PLGA (NHS-PLGA). Postmodification of NHS surface functionality on the NPs with alendronic acid (Aln), a bone-targeting ligand, yielded stable ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) containing NPs that exhibit good serum stability and favorable cytocompatibility. These post-Aln-modified NPs exhibit 8- to 10-fold higher affinity for synthetic and biogenic hydroxyapatite in comparison to NPs where Aln was introduced before NP formation and shorten the T2 relaxation times in both agarose phantoms and fresh spongy bone, thus enabling the interrogation of bone mineral phase in T2-MRI. Finally, by introducing an NIR-dye-modified PLGA during the NP formation step, NP probes that enable the visualization of bone mineral phase in both NIR optical tomography and MRI have been realized. The system presented herein meets many of the criteria for clinical translation and therefore opens new opportunities for bone imaging and targeted therapeutics.
Project description:We measured air broadening in the (30012) ← (00001) carbon dioxide (CO2) band up to J″=50 using frequency-agile rapid scanning cavity ring-down spectroscopy. By using synthetic air samples with varying levels of nitrogen, oxygen, and argon, multi-spectrum fitting allowed for the collisional broadening terms of each major air component to be simultaneously determined in addition to advanced line shape parameters at atmospherically relevant CO2 mixing ratios. These values were compared to broadener-specific line shape parameters from the literature. Fits to measured spectra were also constrained with results from requantized classical molecular dynamic simulations. We show that this approach enables differentiation between narrowing mechanisms in advanced line shape parameters retrieved from experimental spectra of limited signal-to-noise ratio.
Project description:Focusing light deep inside living tissue has not been achieved despite its promise to play a central role in biomedical imaging, optical manipulation and therapy. To address this challenge, internal-guide-star-based wavefront engineering techniques--for example, time-reversed ultrasonically encoded (TRUE) optical focusing--were developed. The speeds of these techniques, however, were limited to no greater than 1 Hz, preventing them from in vivo applications. Here we improve the speed of optical focusing deep inside scattering media by two orders of magnitude, and focus diffuse light inside a dynamic scattering medium having a speckle correlation time as short as 5.6 ms, typical of living tissue. By imaging a target, we demonstrate the first focusing of diffuse light inside a dynamic scattering medium containing living tissue. Since the achieved focusing speed approaches the tissue decorrelation rate, this work is an important step towards in vivo deep tissue noninvasive optical imaging, optogenetics and photodynamic therapy.
Project description:The fluorescent imaging agent IS-001 was determined to be well tolerated in all subjects and has the potential to provide ureter visualization throughout minimally invasive hysterectomy procedures. This study was conducted to evaluate clinical safety and efficacy of a real-time ureter visualization technique for use during hysterectomy surgery. The study drug appears safe, is renally excreted, and allows enhanced ureter visualization when imaged with a clinically approved near-infrared sensitive endoscope. This is a first-in-human study showing preliminary results that the drug is safe and effective during surgery for improved ureter visualization.
Project description:Dynamic micro/nanopatterns provide an effective approach for on-demand tuning of surface properties to realize a smart surface. We report a simple yet versatile strategy for the fabrication of near-infrared (NIR) light-responsive dynamic wrinkles by using a carbon nanotube (CNT)-containing poly(dimethylsiloxane) (PDMS) elastomer as the substrate for the bilayer systems, with various functional polymers serving as the top stiff layers. The high photon-to-thermal energy conversion of CNT leads to the NIR-controlled thermal expansion of the elastic CNT-PDMS substrate, resulting in dynamic regulation of the applied strain (ε) of the bilayer system by the NIR on/off cycle to obtain a reversible wrinkle pattern. The switchable surface topological structures can transfer between the wrinkled state and the wrinkle-free state within tens of seconds via NIR irradiation. As a proof-of-concept application, this type of NIR-driven dynamic wrinkle pattern was used in smart displays, dynamic gratings, and light control electronics.
Project description:SignificanceCritically ill newborns are at risk of brain damage from cerebrovascular disturbances. A cerebral hemodynamic monitoring system would have the potential role to guide targeted intervention.AimTo obtain, in a population of newborn infants, simultaneous near-infrared spectroscopy (NIRS)-based estimates of cerebral tissue oxygen saturation (StO2) and blood flow during variations of carbon dioxide tension (pCO2) levels within physiologic values up to moderate permissive hypercapnia, and to examine if the derived estimate of metabolic rate of oxygen would stay constant, during the same variations.ApproachWe enrolled clinically stable mechanically ventilated newborns at postnatal age >24 h without brain abnormalities at ultrasound. StO2 and blood flow index were measured using a non-invasive device (BabyLux), which combine time-resolved NIRS and diffuse-correlation spectroscopy. The effect of changes in transcutaneous pCO2 on StO2, cerebral blood flow (CBF), and cerebral metabolic rate of oxygen index (tCMRO2i) were estimated.ResultsTen babies were enrolled and three were excluded. Median GA at enrollment was 39 weeks and median weight 2720 g. StO2 increased 0.58% (95% CI 0.55; 0.61, p<0.001), CBF 2% (1.9; 2.3, p<0.001), and tCMRO2 0.3% (0.05; 0.46, p=0.017) per mmHg increase in pCO2.ConclusionsBabyLux device detected pCO2-induced changes in cerebral StO2 and CBF, as expected. The small statistically significant positive relationship between pCO2 and tCMRO2i variation is not considered clinically relevant and we are inclined to consider it as an artifact.