Publication database
Image Enhancement Algorithm of Photoacoustic Tomography Using Active Contour Filtering
The photoacoustic images are obtained from a custom developed linear array photoacoustic tomography system. The biological specimens are imitated by conducting phantom tests in order to retrieve a fully functional photoacoustic image. The acquired image undergoes the active region based contour filtering to remove the noise and accurately segment the object area for further processing. The universal back projection method is used as the image reconstruction algorithm. The active contour filtering is analyzed by evaluating the signal to noise ratio and comparing it with the other filtering methods.
Intraoperative diagnostics and elimination of residual microtumours with plasmonic nanobubbles
Failure of cancer surgery to intraoperatively detect and eliminate microscopic residual disease (MRD) causes lethal recurrence and metastases, and the removal of important normal tissues causes excessive morbidity. Here, we show that a plasmonic nanobubble (PNB), a non-stationary laser pulse-activated nanoevent, intraoperatively detects and eliminates MRD in the surgical bed. PNBs were generated in vivo in head and neck cancer cells by systemically targeting tumours with gold colloids and locally applying near-infrared, low-energy short laser pulses, and were simultaneously detected with an acoustic probe. In mouse models, between 3 and 30 residual cancer cells and MRD (undetectable with current methods) were non-invasively detected up to 4 mm deep in the surgical bed within 1 ms. In resectable MRD, PNB-guided surgery prevented local recurrence and delivered 100% tumour-free survival. In unresectable MRD, PNB nanosurgery improved survival twofold compared with standard surgery. Our results show that PNB-guided surgery and nanosurgery can rapidly and precisely detect and remove MRD in simple intraoperative procedures.
Magneto-elasto-electroporation (MEEP): In-vitro visualization and numerical characteristics
A magnetically controlled elastically driven electroporation phenomenon, or magneto-elasto-electroporation (MEEP), is discovered while studying the interactions between core-shell magnetoelectric nanoparticles (CSMEN) and biological cells in the presence of an a.c. magnetic field. In this paper we report the effect of MEEP observed via a series of in-vitro experiments using core (CoFe2O4)-shell (BaTiO3) structured magnetoelectric nanoparticles and human epithelial cells (HEP2). The cell electroporation phenomenon and its correlation with the magnetic field modulated CSMEN are described in detail. The potential application of CSMEN in electroporation is confirmed by analyzing crystallographic phases, multiferroic properties of the fabricated CSMEN, influences of d.c. and a.c. magnetic fields on the CSMEN and cytotoxicity tests. The mathematical formalism to quantitatively describe the phenomena is also reported. The reported findings provide insights into the underlying MEEP mechanism and demonstrate the utility of CSMEN as an electric pulse-generating nano-probe in electroporation experiments with a potential application toward accurate and efficient targeted cell permeation.
Optoacoustic effect is responsible for laser-induced cochlear responses
Optical stimulation of the cochlea with laser light has been suggested as an alternative to conventional treatment of sensorineural hearing loss with cochlear implants. The underlying mechanisms are controversially discussed: The stimulation can either be based on a direct excitation of neurons, or it is a result of an optoacoustic pressure wave acting on the basilar membrane. Animal studies comparing the intra-cochlear optical stimulation of hearing and deafened guinea pigs have indicated that the stimulation requires intact hair cells. Therefore, optoacoustic stimulation seems to be the underlying mechanism. The present study investigates optoacoustic characteristics using pulsed laser stimulation for in vivo experiments on hearing guinea pigs and pressure measurements in water. As a result, in vivo as well as pressure measurements showed corresponding signal shapes. The amplitude of the signal for both measurements depended on the absorption coefficient and on the maximum of the first time-derivative of laser pulse power (velocity of heat deposition). In conclusion, the pressure measurements directly demonstrated that laser light generates acoustic waves, with amplitudes suitable for stimulating the (partially) intact cochlea. These findings corroborate optoacoustic as the basic mechanism of optical intra-cochlear stimulation.
Roles of reactive oxygen species in UVA-induced oxidation of 5,6-dihydroxyindole-2-carboxylic acid-melanin as studied by differential spectrophotometric method
Eumelanin photoprotects pigmented tissues from ultraviolet (UV) damage. However, UVA-induced tanning seems to result from the photooxidation of preexisting melanin and does not contribute to photoprotection. We investigated the mechanism of UVA-induced degradation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-melanin taking advantage of its solubility in a neutral buffer and using a differential spectrophotometric method to detect subtle changes in its structure. Our methodology is suitable for examining the effects of various agents that interact with reactive oxygen species (ROS) to determine how ROS is involved in the UVA-induced oxidative modifications. The results show that UVA radiation induces the oxidation of DHICA to indole-5,6-quinone-2-carboxylic acid in eumelanin, which is then cleaved to form a photodegraded, pyrrolic moiety and finally to form free pyrrole-2,3,5-tricarboxylic acid. The possible involvement of superoxide radical and singlet oxygen in the oxidation was suggested. The generation and quenching of singlet oxygen by DHICA-melanin was confirmed by direct measurements of singlet oxygen phosphorescence.
Sensitive Water Probing through Nonlinear Photon Upconversion of Lanthanide-Doped Nanoparticles
Lanthanide-doped upconversion nanoparticles have received growing attention in the development of low-background, highly sensitive and selective sensors. Here, we report a water probe based on ligand-free NaYF4:Yb/Er nanoparticles, utilizing their intrinsically nonlinear upconversion process. The water molecule sensing was realized by monitoring the upconversion emission quenching, which is mainly attributed to efficient energy transfer between upconversion nanoparticles and water molecules as well as water-absorption-induced excitation energy attenuation. The nonlinear upconversion process, together with power function relationship between upconversion emission intensity and excitation power density, offers a sensitive detection of water content down to 0.008 vol % (80 ppm) in an organic solvent. As an added benefit, we show that noncontact detection of water can be achieved just by using water attenuation effect. Moreover, these upconversion nanoparticle based recyclable probes should be particularly suitable for real-time and long-term water monitoring, due to their superior chemical and physical stability. These results could provide insights into the design of upconversion nanoparticle based sensors.
Enhancement of objects in photoacoustic tomography using selective filtering
Here we developed a real-time photoacoustic tomography (PAT) imaging acquisition device based on the linear array transducer utilized on ultrasonic devices. Also, we produced a phantom including diverse contrast media and acquired PAT imaging as the light source wavelength was changing to see if the contrast media reacted. Indocyanine green showed the highest reaction around the 800-nm band, methylene blue demonstrated the same in the 750-nm band, and gold nanoparticle showed the same in the 700-nm band. However, in the case of superparamagnetic iron oxide, we observed not reaction within the wavelength bands used herein to obtain imaging. Moreover, we applied selective filtering to the acquired PAT imaging to remove noise from around and reinforce the object’s area. Consequentially, we could see the object area in the imaging was effectively detected and the image noise was removed.
Optogenetic control of insulin secretion by pancreatic β-cells in vitro and in vivo
The present study assessed the ability of optogenetics techniques to provide a better understanding of the control of insulin secretion, particularly regarding pancreatic β-cell function in homeostasis and pathological conditions such as diabetes mellitus (DM). We used optogenetics to investigate whether insulin secretion and blood glucose homeostasis could be controlled by regulating intracellular calcium ion concentrations ([Ca2+]i) in a mouse pancreatic β-cell line (MIN6) transfected with the optogenetic protein channelrhodopsin-2 (ChR2). The ChR2-transfected MIN6 (ChR2-MIN6) cells secreted insulin following irradiation with a laser (470 nm). The increase in [Ca2+]i was accompanied by elevated levels of messenger RNAs that encode calcium/calmodulin-dependent protein kinase II delta and adenylate cyclase 1. ChR2-MIN6 cells suspended in matrigel were inoculated into streptozotocin-induced diabetic mice that were then subjected to a glucose tolerance test. Laser irradiation of these mice caused a significant decrease in blood glucose, and the irradiated implanted cells expressed insulin. These findings demonstrate the power of optogenetics to precisely and efficiently controlled insulin secretion by pancreatic β-cells ‘on demand', in contrast to techniques using growth factors or chemical inducers. Optogenetic technology shows great promise for understanding the mechanisms of glucose homeostasis and for developing treatments for metabolic diseases such as DM.
On-demand intracellular amplification of chemoradiation with cancer-specific plasmonic nanobubbles
Chemoradiation-resistant cancers limit treatment efficacy and safety. We show here the cancer cell–specific, on-demand intracellular amplification of chemotherapy and chemoradiation therapy via gold nanoparticle– and laser pulse–induced mechanical intracellular impact. Cancer aggressiveness promotes the clustering of drug nanocarriers and gold nanoparticles in cancer cells. This cluster, upon exposure to a laser pulse, generates a plasmonic nanobubble, the mechanical explosion that destroys the host cancer cell or ejects the drug into its cytoplasm by disrupting the liposome and endosome. The same cluster locally amplifies external X-rays. Intracellular synergy of the mechanical impact of plasmonic nanobubble, ejected drug and amplified X-rays improves the efficacy of standard chemoradiation in resistant and aggressive head and neck cancer by 100-fold in vitro and 17-fold in vivo, reduces the effective entry doses of drugs and X-rays to 2–6% of their clinical doses and efficiently spares normal cells. The developed quadrapeutics technology combines four clinically validated components and transforms a standard macrotherapy into an intracellular on-demand theranostic microtreatment with radically amplified therapeutic efficacy and specificity.
A Novel Method for Direct Nondestructive Diagnosis of Caries Affected Tooth Surfaces by Laser Multiphoton Ionization
A new nondestructive analytical method for diagnosis of tooth caries is presented. The method is based on the Multiphoton Ionization (MPI) fast conductivity signals measured from tooth surfaces. The signals are acquired for a series of laser wavelengths, thus obtaining full MPI spectra. The results indicate a good correlation between the MPI results and the degree of severity of the caries, as diagnosed using traditional inspection. Moreover, the spectral information can be reduced (using least squares fitting) to a single parameter that provides an objective quantitative estimation of the caries severity. The MPI data can be obtained for tiny points on the dental surface and it is suggested that mapping is possible by scanning method.