Bright Chromenylium Polymethine Dyes Enable Fast, Four-Color In Vivo Imaging with Shortwave Infrared Detection.
Journal of the American Chemical Society
2021; 143 (18): 6836–46
Shortwave infrared polymethine fluorophores matched to excitation lasers enable non-invasive, multicolour in vivo imaging in real time
2020; 12 (12): 1123-+
Optical imaging within the shortwave infrared (SWIR, 1000-2000 nm) region of the electromagnetic spectrum has enabled high-resolution and high-contrast imaging in mice, non-invasively. Polymethine dyes, with their narrow absorption spectra and high absorption coefficients, are optimal probes for fast and multiplexed SWIR imaging. Here, we expand upon the multiplexing capabilities in SWIR imaging by obtaining brighter polymethine dyes with varied excitation wavelengths spaced throughout the near-infrared (700-1000 nm) region. Building on the flavylium polymethine dye scaffold, we explored derivatives with functional group substitution at the 2-position, deemed chromenylium polymethine dyes. The reported dyes have reduced nonradiative rates and enhanced emissive properties, enabling non-invasive imaging in mice in a single color at 300 fps and in three colors at 100 fps. Combined with polymethine dyes containing a red-shifted julolidine flavylium heterocycle and indocyanine green, distinct channels with well-separated excitation wavelengths provide non-invasive video-rate in vivo imaging in four colors.
View details for DOI 10.1021/jacs.0c11599
View details for PubMedID 33939921
Shortwave Infrared Imaging with J-Aggregates Stabilized in Hollow Mesoporous Silica Nanoparticles
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2019; 141 (32): 12475–80
High-resolution, multiplexed experiments are a staple in cellular imaging. Analogous experiments in animals are challenging, however, due to substantial scattering and autofluorescence in tissue at visible (350-700 nm) and near-infrared (700-1,000 nm) wavelengths. Here, we enable real-time, non-invasive multicolour imaging experiments in animals through the design of optical contrast agents for the shortwave infrared (SWIR, 1,000-2,000 nm) region and complementary advances in imaging technologies. We developed tunable, SWIR-emissive flavylium polymethine dyes and established relationships between structure and photophysical properties for this class of bright SWIR contrast agents. In parallel, we designed an imaging system with variable near-infrared/SWIR excitation and single-channel detection, facilitating video-rate multicolour SWIR imaging for optically guided surgery and imaging of awake and moving mice with multiplexed detection. Optimized dyes matched to 980 nm and 1,064 nm lasers, combined with the clinically approved indocyanine green, enabled real-time, three-colour imaging with high temporal and spatial resolutions.
View details for DOI 10.1038/s41557-020-00554-5
View details for Web of Science ID 000579693400004
View details for PubMedID 33077925
View details for PubMedCentralID PMC7680456
Flavylium Polymethine Fluorophores for Near- and Shortwave Infrared Imaging
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2017; 56 (42): 13126–29
Tissue is translucent to shortwave infrared (SWIR) light, rendering optical imaging superior in this region. However, the widespread use of optical SWIR imaging has been limited, in part, by the lack of bright, biocompatible contrast agents that absorb and emit light above 1000 nm. J-Aggregation offers a means to transform stable, near-infrared (NIR) fluorophores into red-shifted SWIR contrast agents. Here we demonstrate that J-aggregates of NIR fluorophore IR-140 can be prepared inside hollow mesoporous silica nanoparticles (HMSNs) to result in nanomaterials that absorb and emit SWIR light. The J-aggregates inside PEGylated HMSNs are stable for multiple weeks in buffer and enable high resolution imaging in vivo with 980 nm excitation.
View details for DOI 10.1021/jacs.9b05195
View details for Web of Science ID 000481563500008
View details for PubMedID 31353894
View details for PubMedCentralID PMC6746239
Absence of Radiographic Abnormalities in Nursemaid's Elbows
JOURNAL OF PEDIATRIC ORTHOPAEDICS
2014; 34 (4): 426–31
Bright fluorophores in the near-infrared and shortwave infrared (SWIR) regions of the electromagnetic spectrum are essential for optical imaging in vivo. In this work, we utilized a 7-dimethylamino flavylium heterocycle to construct a panel of novel red-shifted polymethine dyes, with emission wavelengths from 680 to 1045 nm. Photophysical characterization revealed that the 1- and 3-methine dyes display enhanced photostability and the 5- and 7-methine dyes exhibit exceptional brightness for their respective spectral regions. A micelle formulation of the 7-methine facilitated SWIR imaging in mice. This report presents the first polymethine dye designed and synthesized for SWIR in vivo imaging.
View details for DOI 10.1002/anie.201706974
View details for Web of Science ID 000412189700061
View details for PubMedID 28806473
Disagreement exists between physicians on the usefulness of a prereduction radiograph for diagnosis and treatment of nursemaid's elbows in children. Some evidence suggests that nursemaid's elbows have identifying features on radiographs. This study compares the radiographs of nursemaid's elbows to normal, control elbows in children and hypothesizes that differentiating features do not exist on radiograph.For this retrospective case-control study, hospital billing records were searched to identify all patients under age 6 treated with closed reduction for a nursemaid's elbow between November 2005 and October 2009. Twenty-seven nursemaid's elbows were age-matched and sex-matched to 27 normal "comparison view," control elbows. Radiocapitellar line offset, proximal radial length, anterior fat pad angle, and visibility of the posterior fat pad were measured on the radiographs by 2 raters. Their interrater reliability was assessed with intraclass correlations, and the nursemaid's and control elbow measures were compared using Wilcoxon tests.Nursemaid's elbows and healthy control elbows did not differ significantly in offset of the radiocapitellar line from the capitellum center on anteroposterior (P=0.49) or lateral views (P=0.67), in proximal radial length (P=0.95), anterior fat pad angle (P=0.49), or posterior fat pad visibility (P=1.00) on lateral views.Nursemaid's elbows are indistinguishable from healthy elbows on radiograph. Thus, the term "radial head subluxation" appears to be a misnomer, and prereduction radiographs should only be used to eliminate the possibility of fracture. From a radiologic perspective, nursemaid's elbows remain a diagnosis of exclusion.Therapeutic Level III-retrospective comparative study.
View details for Web of Science ID 000337745100011
View details for PubMedID 24276229