The effects of laser repetition rate on femtosecond laser ablation of dry bone: a thermal and LIBS study.

The aim of this study is to understand the effect of varying laser repetition rate on thermal energy accumulation and dissipation as well as femtosecond Laser Induced Breakdown Spectroscopy (fsLIBS) signals, which may help create the framework for clinical translation of femtosecond lasers for surgical procedures. We study the effect of repetition rates on ablation widths, sample temperature, and LIBS signal of bone. SEM images were acquired to quantify the morphology of the ablated volume and fsLIBS was performed to characterize changes in signal intensity and background. We also report for the first time experimentally measured temperature distributions of bone irradiated with femtosecond lasers at repetition rates below and above carbonization conditions. While high repetition rates would allow for faster cutting, heat accumulation exceeds heat dissipation and results in carbonization of the sample. At repetition rates where carbonization occurs, the sample temperature increases to a level that is well above the threshold for irreversible cellular damage. These results highlight the importance of the need for careful selection of the repetition rate for a femtosecond laser surgery procedure to minimize the extent of thermal damage to surrounding tissues and prevent misclassification of tissue by fsLIBS analysis.

Preliminary fsLIBS study on bone tumors.

The aim of this study is to evaluate the capability of femtosecond Laser Induced Breakdown Spectroscopy (fsLIBS) to discriminate between normal and cancerous bone, with implications to femtosecond laser surgery procedures. The main advantage of using femtosecond lasers for surgery is that the same laser that is being used to ablate can also be used for a feedback system to prevent ablation of certain tissues. For bone tumor removal, this technique has the potential to reduce the number of repeat surgeries that currently must be performed due to incomplete removal of the tumor mass. In this paper, we performed fsLIBS on primary bone tumor, secondary tumor in bone, and normal bone. These tissues were excised from consenting patients and processed through the UC Davis Cancer Center Biorepository. For comparison, each tumor sample had a matched normal bone sample. fsLIBS was performed to characterize the spectral signatures of each tissue type. A minimum of 20 spectra were acquired for each sample. We did not detect significant differences between the fsLIBS spectra of secondary bone tumors and their matched normal bone samples, likely due to the heterogeneous nature of secondary bone tumors, with normal and cancerous tissue intermingling. However, we did observe an increase in the fsLIBS magnesium peak intensity relative to the calcium peak intensity for the primary bone tumor samples compared to the normal bone samples. These results show the potential of using femtosecond lasers for both ablation and a real-time feedback control system for treatment of primary bone tumors.

Computed Cerenkov luminescence yields for radionuclides used in biology and medicine.

Cerenkov luminescence imaging is an emerging biomedical imaging modality that takes advantage of the optical Cerenkov photons emitted following the decay of radionuclides in dielectric media such as tissue. Cerenkov radiation potentially allows many biomedically-relevant radionuclides, including all positron-emitting radionuclides, to be imaged in vivo using sensitive CCD cameras. Cerenkov luminescence may also provide a means to deliver light deep inside tissue over a sustained period of time using targeted radiotracers. This light could be used for photoactivation, including photorelease of therapeutics, photodynamic therapy and photochemical internalization. Essential to assessing the feasibility of these concepts, and the design of instrumentation designed for detecting Cerenkov radiation, is an understanding of the light yield of different radionuclides in tissue. This is complicated by the dependence of the light yield on refractive index and the volume of the sample being interrogated. Using Monte Carlo simulations, in conjunction with step-wise use of the Frank-Tamm equation, we studied forty-seven different radionuclides and show that Cerenkov light yields in tissue can be as high as a few tens of photons per nuclear decay for a wavelength range of 400-800 nm. The dependency on refractive index and source volume is explored, and an expression for the scaling factor necessary to compute the Cerenkov yield in any arbitrary spectral band is given. This data will be of broad utility in guiding the application of Cerenkov radiation emitted from biomedical radionuclides.

Characterization of femtosecond laser-induced breakdown spectroscopy (fsLIBS) and applications for biological samples.

We characterize the femtosecond laser-induced breakdown spectroscopy (fsLIBS) signal for biological tissues as a function of different excitation parameters with femtosecond laser systems. These parameters include laser energy, depth of focus, and number of pulses per focal volume. We used femtosecond laser pulses of 800 nm and energy between 25 and 123 µJ to generate LIBS signals in biological tissues. As expected, we observed a linear increase in the fsLIBS intensity as a function of the laser energy. In addition, we show that moving the beam out of focus and the presence of overlapping pulses on the same focal area leads to a decrease in fsLIBS intensity due to changes in focal spot size. We also demonstrate that fsLIBS can distinguish between different biological tissue samples.

In vivo Cerenkov luminescence imaging: a new tool for molecular imaging.

Cerenkov radiation is a phenomenon where optical photons are emitted when a charged particle moves faster than the speed of light for the medium in which it travels. Recently, we and others have discovered that measurable visible light due to the Cerenkov effect is produced in vivo following the administration of ß-emitting radionuclides to small animals. Furthermore, the amounts of injected activity required to produce a detectable signal are consistent with small-animal molecular imaging applications. This surprising observation has led to the development of a new hybrid molecular imaging modality known as Cerenkov luminescence imaging (CLI), which allows the spatial distribution of biomolecules labelled with ß-emitting radionuclides to be imaged in vivo using sensitive charge-coupled device cameras. We review the physics of Cerenkov radiation as it relates to molecular imaging, present simulation results for light intensity and spatial distribution, and show an example of CLI in a mouse cancer model. CLI allows many common radiotracers to be imaged in widely available in vivo optical imaging systems, and, more importantly, provides a pathway for directly imaging ß(-)-emitting radionuclides that are being developed for therapeutic applications in cancer and that are not readily imaged by existing methods.