Proof of concept for the sapphire scalpel combining tissue dissection and optical diagnosis.

OBJECTIVES: The development of compact diagnostic probes and instruments with an ability to direct access to organs and tissues and integration of these instruments into surgical workflows is an important task of modern physics and medicine. The need for such tools is essential for surgical oncology, where intraoperative visualization and demarcation of tumor margins define further prognosis and survival of patients. In this paper, the possible solution for this intraoperative imaging problem is proposed and its feasibility to detect tumorous tissue is studied experimentally. METHODS: For this aim, the sapphire scalpel was developed and fabricated using the edge-defined film-fed growth technique aided by mechanical grinding, polishing, and chemical sharpening of the cutting edge. It possesses optical transparency, mechanical strength, chemical inertness, and thermal resistance alongside the presence of the as-grown hollow capillary channels in its volume for accommodating optical fibers. The rounding of the cutting edge exceeds the same for metal scalpels and can be as small as 110 nm. Thanks to these features, sapphire scalpel combines tissue dissection with light delivering and optical diagnosis. The feasibility for the tumor margin detection was studied, including both gelatin-based tissue phantoms and ex vivo freshly excised specimens of the basal cell carcinoma from humans and the glioma model 101.8 from rats. These tumors are commonly diagnosed either non-invasively or intraoperatively using different modalities of fluorescence spectroscopy and imaging, which makes them ideal candidates for our feasibility test. For this purpose, fiber-based spectroscopic measurements of the backscattered laser radiation and the fluorescence signals were carried out in the visible range. RESULTS: Experimental studies show the feasibility of the proposed sapphire scalpel to provide a 2-mm-resolution of the tumor margins' detection, along with an ability to distinguish the tumor invasion region, which results from analysis of the backscattered optical fields and the endogenous or exogenous fluorescence data. CONCLUSIONS: Our findings justified a strong potential of the sapphire scalpel for surgical oncology. However, further research and engineering efforts are required to optimize the sapphire scalpel geometry and the optical diagnosis protocols to meet the requirements of oncosurgery, including diagnosis and resection of neoplasms with different localizations and nosologies.

In situ terahertz monitoring of an ice ball formation during tissue cryosurgery: a feasibility test.

SIGNIFICANCE: Uncontrolled cryoablation of tissues is a strong reason limiting the wide application of cryosurgery and cryotherapy due to the certain risks of unpredicted damaging of healthy tissues. The existing guiding techniques are unable to be applied in situ or provide insufficient spatial resolution. Terahertz (THz) pulsed spectroscopy (TPS) based on sensitivity of THz time-domain signal to changes of tissue properties caused by freezing could form the basis of an instrument for observation of the ice ball formation. AIM: The ability of TPS for in situ monitoring of tissue freezing depth is studied experimentally. APPROACH: A THz pulsed spectrometer operated in reflection mode and equipped with a cooled sample holder and ex vivo samples of bovine visceral adipose tissue is applied. Signal spectrograms are used to analyze the changes of THz time-domain signals caused by the interface between frozen and unfrozen tissue parts. RESULTS: Experimental observation of TPS signals reflected from freezing tissue demonstrates the feasibility of TPS to detect ice ball formation up to 657-µm depth. CONCLUSIONS: TPS could become the promising instrument for in situ control of cryoablation, enabling observation of the freezing front propagation, which could find applications in various fields of oncology, regenerative medicine, and THz biophotonics.

Optimization of sapphire capillary needles for interstitial and percutaneous laser medicine.

Sapphire capillary needles fabricated by edge-defined film-fed growth (EFG) technique hold strong potential in laser thermotherapy and photodynamic therapy, thanks to the advanced physical properties of sapphire. These needles feature an as-grown optical quality, their length is tens of centimeters, and they contain internal capillary channels, with open or closed ends. They can serve as optically transparent bearing elements with optical fibers introduced into their capillary channels in order to deliver laser radiation to biological tissues for therapeutic and, in some cases, diagnostic purposes. A potential advantage of the EFG-grown sapphire needles is associated with an ability to form the tip of a needle with complex geometry, either as-grown or mechanically treated, aimed at controlling the output radiation pattern. In order to examine a potential of the radiation pattern shaping, we present a set of fabricated sapphire needles with different tips. We studied the radiation patterns formed at the output of these needles using a He-Ne laser as a light source, and used intralipid-based tissue phantoms to proof the concept experimentally and the Monte-Carlo modeling to proof it numerically. The observed results demonstrate a good agreement between the numerical and experimental data and reveal an ability to control within wide limits the direction of tissue exposure to light and the amount of exposed tissue by managing the sapphire needle tip geometry.

Terahertz spectroscopy of gelatin-embedded human brain gliomas of different grades: a road toward intraoperative THz diagnosis.

We applied terahertz (THz)-pulsed spectroscopy to study ex vivo the refractive index and absorption coefficient of human brain gliomas featuring different grades, as well as perifocal regions containing both intact and edematous tissues. Glioma samples from 26 patients were considered and analyzed according to further histological examination. In order to fix tissues for the THz measurements, we applied gelatin embedding, which allows for sustaining their THz response unaltered, as compared to that of the freshly excised tissues. We observed a statistical difference between the THz optical constants of intact tissues and gliomas of grades I to IV, while the response of edema was similar to that of tumor. The results of this paper justify a potential of THz technology in the intraoperative label-free diagnosis of human brain gliomas for ensuring the gross-total resection.