Cancer radiotherapy based on femtosecond IR laser-beam filamentation yielding ultra-high dose rates and zero entrance dose.

Since the invention of cancer radiotherapy, its primary goal has been to maximize lethal radiation doses to the tumor volume while keeping the dose to surrounding healthy tissues at zero. Sadly, conventional radiation sources (γ or X rays, electrons) used for decades, including multiple or modulated beams, inevitably deposit the majority of their dose in front or behind the tumor, thus damaging healthy tissue and causing secondary cancers years after treatment. Even the most recent pioneering advances in costly proton or carbon ion therapies can not completely avoid dose buildup in front of the tumor volume. Here we show that this ultimate goal of radiotherapy is yet within our reach: Using intense ultra-short infrared laser pulses we can now deposit a very large energy dose at unprecedented microscopic dose rates (up to 10(11) Gy/s) deep inside an adjustable, well-controlled macroscopic volume, without any dose deposit in front or behind the target volume. Our infrared laser pulses produce high density avalanches of low energy electrons via laser filamentation, a phenomenon that results in a spatial energy density and temporal dose rate that both exceed by orders of magnitude any values previously reported even for the most intense clinical radiotherapy systems. Moreover, we show that (i) the type of final damage and its mechanisms in aqueous media, at the molecular and biomolecular level, is comparable to that of conventional ionizing radiation, and (ii) at the tumor tissue level in an animal cancer model, the laser irradiation method shows clear therapeutic benefits.

Improved detection sensitivity of D-mannitol crystalline phase content using differential spectral phase shift terahertz spectroscopy measurements.

We report quantitative measurement of the relative proportion of δ- and ß-D-mannitol crystalline phases inserted into polyethylene powder pellets, obtained by time-domain terahertz spectroscopy. Nine absorption bands have been identified from 0.2 THz to 2.2 THz. The best quantification of the δ-phase proportion is made using the 1.01 THz absorption band. Coherent detection allows using the spectral phase shift of the transmitted THz waveform to improve the detection sensitivity of the relative δ-phase proportion. We argue that differential phase shift measurements are less sensitive to samples' defects. Using a linear phase shift compensation for pellets of slightly different thicknesses, we were able to distinguish a 0.5% variation in δ-phase proportion.

Fabrication and THz loss measurements of porous subwavelength fibers using a directional coupler method.

We report several strategies for the fabrication of porous subwavelength fibers using low density Polyethylene plastic for low-loss terahertz light transmission applications. We also characterize transmission losses of the fabricated fibers in terahertz using a novel non-destructive directional coupler method. Within this method a second fiber is translated along the length of the test fiber to probe the power attenuation of a guided mode. The method is especially suitable for measuring transmission losses through short fiber segments, a situation in which standard cutback method is especially difficult to perform. We demonstrate experimentally that introduction of porosity into a subwavelength rod fiber, further reduces its transmission loss by as much as a factor of 10. The lowest fiber loss measured in this work is 0.01 cm(-1) and it is exhibited by the 40% porous subwavelength fiber of diameter 380 microm. For comparison, the loss of a rod-in-the-air subwavelength fiber of a similar diameter was measured to be approximately 0.1 cm(-1), while the bulk loss of a PE plastic used in the fabrication of such fibers is >or= 1 cm(-1). Finally, we present theoretical studies of the optical properties of individual subwavelength fibers and a directional coupler. From these studies we conclude that coupler setup studied in this paper also acts as a low pass filter with a cutoff frequency around 0.3 THz. Considering that the spectrum of a terahertz source used in this work falls off rapidly below 0.25 THz, the reported loss measurements are, thus, the bolometer averages over the approximately 0.25 THz-0.3 THz region.

A new two-photon-sensitive block copolymer nanocarrier.

Easily disrupted: Micelles of a new amphiphilic block copolymer that bear coumarin groups are sensitive to near infrared light by two-photon absorption of the chromophore. Disruption of the micelles under irradiation at 794 nm results in release of both photocleaved coumarin and encapsulated nile red from the hydrophobic core of micelle into aqueous solution, which results in opposing changes in fluorescence emission intensity.

Two-photon absorption cross section of excited phthalocyanines by a femtosecond Ti-sapphire laser.

In the past few years, photodynamic therapy (PDT) has become a major treatment for neovascular age-related macular degeneration (AMD) in which there is abnormal growth of choroidal neovasculature (CNV) that eventually obscures central vision, leading to blindness. However, one of the main limitations of current PDT is the relatively low specificity of the photosensitizer (PS) and light for pathological tissue which may induce damage to adjacent healthy tissue. An alternative approach to circumvent the specificity limitation is to improve the irradiation process. In particular two photon (2-gamma) excitation promises a more precise illumination of the target tissue. PS are activated by the simultaneous absorption of 2-gamma delivered by ultra-fast pulses of near infrared light. In order to evaluate the efficiency of phthalocyanine (Pc) dyes for 2-gamma absorption we measured 2-gamma absorption cross sections (sigma(2)) of a number of metalated Pc (MPc) dyes at lambda(ex) = 800 nm using a femtosecond laser. The studied Pc molecules vary by the type of the central metal ion (Al or Zn) and the number of peripheral sulfo substituents (MPcS). Each MPc dye of our series shows an improved 2-gamma absorption sigma(2) as compared to that obtained for Photofrin (3.1 +/- 0.1 GM, with 1 GM = 10(-50) cm(4) s photon(-1) mol(-1)), the PS currently approved for 1-gamma PDT. Our data show an 2.5-fold enhancement for AlPcCl, AlPcS(2adj) and ZnPcS(3)C(9), up to 10-fold (28.6 +/- 0.72 GM) for the ZnPcS(4) dye relative to Photofrin. These findings confirm the efficiency of Pc for 2-gamma absorption processes and represent the first detailed comparison study of 2-gamma absorption sigma(2) between Photofrin and Pc dyes.

On the dynamic viscous permeability tensor symmetry.

Based on a direct generalization of a proof given by Torquato for symmetry property in static regime, this express letter clarifies the reasons why the dynamic permeability tensor is symmetric for spatially periodic structures having symmetrical axes which do not coincide with orthogonal pairs being perpendicular to the axis of three-, four-, and sixfold symmetry. This somewhat nonintuitive property is illustrated by providing detailed numerical examples for a hexagonal lattice of solid cylinders in the asymptotic and frequency dependent regimes. It may be practically useful for numerical implementation validation and/or convergence assessment.

Impedance measurements around grazing incidence for nonlocally reacting thin porous layers.

For locally reacting materials with a constant surface impedance, a classical method based on the work of Chien and Soroka [J. Sound Vib. 43, 9-20 (1975)] for measuring this impedance in situ around grazing incidence is currently used. A generalization of this work to include thin nonlocally reacting materials with a surface impedance noticeably dependent on the angle of incidence is performed. It is shown that the model by Chien and Soroka can be used, though the constant surface impedance must be replaced by the impedance at grazing incidence for the evaluation of the numerical distance. Measurements performed on a thin porous layer using this method are compared with measurements performed using the near-field acoustical holography method [M. Tamura, J. Acoust. Soc. Am. 88, 2259-2264 (1990)]. Other measurements performed on a fibrous layer are in good agreement with the predicted values of the impedance at grazing incidence.