Characterization of Triphenylamine and Ferrocenyl Donor-π-donor Vinyl BODIPY Derivatives as Photoacoustic Contrast Agents.

The photophysical and electrochemical properties for a series of BODIPY dyes with incremental 3- and 3,5-vinyl conjugation, as well as incremental electron-donating groups (anisole < triphenylamine < ferrocenyl), are presented. Insight into the influence of each vinyl-conjugated electron-donating group on both vis-NIR absorption and fluorescence emission properties is provided. These trends are further corroborated by density functional theory computational analysis. Two of this series containing the 3,5-bis(vinyltriphenylamine) and 3,5-bis(vinylferrocenyl) substituents exhibit significant absorption cross sections in the biological transparency window justifying further investigation of their photoacoustic emission properties via both optical photoacoustic z-scan and photoacoustic tomography experiments. Both the 3,5-bis(vinyltriphenylamine) and 3,5-bis(vinylferrocenyl) substituted BODIPY dyes exhibit quantitative photoacoustic quantum yields. Relative to the commercially available methylene blue and indocyanine green molecular photoacoustic contrast agents, the 3,5-bis(vinyltriphenylamine)-derived BODIPY exhibits the greatest photoacoustic emission and contrast upon excited-state absorption at 685 nm excitation at a low power laser fluence (<20 mJ cm-2 ).

Photophysical and Photoacoustic Properties of π-Extended Curcumin Dyes. Effects of the Terminal Dimethylamino Electron-donor and the Bridging Aryl Ring.

The synthesis, photophysical and photoacoustic characterization for a series of nine π-extended quadrupolar curcumin dyes is presented. A systematic evaluation of the π-bridging unit including the p-phenyl, naphth-4-yl, thien-2-yl and hybrid 4-naphthathien-2-yl groups is presented. Furthermore, evaluation of the strongly donating donor-π-acceptor-π-donor quadrupolar dimethylamino terminated derivatives is also included. Select dyes exhibit excited state absorption at increased laser fluence which translates to the production of a nonlinear enhanced photoacoustic response. In particular, the bis-4-dimethylaminonaphtha-2-thien-5-yl curcuminBF2 contrast agent DMA-5 exhibits an excellent molar photoacoustics (PA) emission at both low (9.4 × 103  V M-1 ) and high (1.47 × 105  V M-1 ) laser fluence which is confirmed by its strong contrast by photoacoustic tomography (PAT). In summary, the strong absorbance and enhanced photoacoustic properties of naphthyl and thienyl curcuminoids here presented provides great promise for future photoacoustic imaging applications as demonstrated by preliminary PAT studies.

Characterization of a NIR absorbing thienyl curcumin contrast agent for photoacoustic imaging.

The synthesis and characterization of a bis(2-dimethylaminothien-5-yl)curcumin boron difluoride chromophore is presented. Photophysical, electrochemical and computational investigations establish the properties of its absorption in the Vis-NIR spectral range relative to established curcumin dyes. Application of this thienyl curcumin dye as a photoacoustic contrast agent is investigated against the dicarbocyanine Cy5 dye in the 675-735 nm excitation range.

Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.

In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala, while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures.

Photophysical and Photoacoustic Properties of Quadrupolar Borondifluoride Curcuminoid Dyes.

The synthesis and characterization of a series of donor-π-acceptor-π-donor (D-A-D) curcuminoid molecules is presented herein that incorporates π-extended aryl and electron-donating amino terminal functionalization. Computational evaluation shows these molecules possess quadrupolar character with the lowest energy transitions displaying high molar extinction coefficients with broad tunability through manipulation of terminal donating groups. Consistent with their quadrupolar nature, these molecules show varying degrees of solvatochromic behavior in both their absorption and emission spectra, which has been analyzed by Lippert-Mataga and Kamlet-Taft analysis. Photophysical and photoacoustic (PA) properties of these molecules have been investigated by the optical photoacoustic z-scan (OPAZ) method. Selected curcuminoid molecules display nonlinear behavior at a high laser fluence through excited state absorption that translates to the production of an enhanced photoacoustic emission. A relative comparison of "molar PA emission" is also presented with the crystal violet linear optical absorbing/linear PA emitting system being utilized as a standard reference material for OPAZ experiments. Furthermore, PA tomography experiments are presented to illustrate the enhanced PA contrast obtainable via an excited state absorption.

Digital holographic microscopy for longitudinal volumetric imaging of growth and treatment response in three-dimensional tumor models.

We report the use of digital holographic microscopy (DHM) as a viable microscopy approach for quantitative, nondestructive longitudinal imaging of in vitro three-dimensional (3-D) tumor models. Following established methods, we prepared 3-D cultures of pancreatic cancer cells in overlay geometry on extracellular matrix beds and obtained digital holograms at multiple time points throughout the duration of growth. The holograms were digitally processed and the unwrapped phase images were obtained to quantify the nodule thickness over time under normal growth and in cultures subject to chemotherapy treatment. In this manner, total nodule volumes are rapidly estimated and demonstrated here to show contrasting time-dependent changes during growth and in response to treatment. This work suggests the utility of DHM to quantify changes in 3-D structure over time and suggests the further development of this approach for time-lapse monitoring of 3-D morphological changes during growth and in response to treatment that would otherwise be impractical to visualize.

Shining light on the dark side of imaging: excited state absorption enhancement of a bis-styryl BODIPY photoacoustic contrast agent.

A first approach toward understanding the targeted design of molecular photoacoustic contrast agents (MPACs) is presented. Optical and photoacoustic Z-scan spectroscopy was used to identify how nonlinear (excited-state) absorption contributes to enhancing the photoacoustic emission of the curcuminBF2 and bis-styryl (MeOPh)2BODIPY dyes relative to Cy3.