Improving maximal safe brain tumor resection with photoacoustic remote sensing microscopy

Abstract

Malignant brain tumors are among the deadliest neoplasms with the lowest survival rates of any cancer type. In considering surgical tumor resection, suboptimal extent of resection is linked to poor clinical outcomes and lower overall survival rates. Currently available tools for intraoperative histopathological assessment require an average of 20 min processing and are of limited diagnostic quality for guiding surgeries. Consequently, there is an unaddressed need for a rapid imaging technique to guide maximal resection of brain tumors. Working towards this goal, presented here is an all optical non-contact label-free reflection mode photoacoustic remote sensing (PARS) microscope. By using a tunable excitation laser, PARS takes advantage of the endogenous optical absorption peaks of DNA and cytoplasm to achieve virtual contrast analogous to standard hematoxylin and eosin (H&E) staining. In conjunction, a fast 266 nm excitation is used to generate large grossing scans and rapidly assess small fields in real-time with hematoxylin-like contrast. Images obtained using this technique show comparable quality and contrast to the current standard for histopathological assessment of brain tissues. Using the proposed method, rapid, high-throughput, histological-like imaging was achieved in unstained brain tissues, indicating PARS’ utility for intraoperative guidance to improve extent of surgical resection.

Single acquisition label-free histology-like imaging with dual-contrast photoacoustic remote sensing microscopy

“…In this implementation, we use a 50-kHz UV excitation, which provides emulated H&E images substantially faster than the 1-kHz tunable source used in previous studies. 17,18 For example, the image presented in Fig. 5 is captured in under 15 min with the proposed dual-contrast system, whereas it would require nearly 13 h to capture with the previously reported tunable system.…”

“… 14 Moreover, PARS may provide chromophore-specific contrast by selecting excitation wavelengths to target unique biomolecule absorption spectra. 15 – 18 Applied to histological imaging, PARS has successfully used UV excitation to capture nuclear structures. 15 – 21 This technique is efficacious in providing hematoxylin-like contrast in frozen sections and paraffin-embedded blocks and sections.…”

“… 15 – 18 Applied to histological imaging, PARS has successfully used UV excitation to capture nuclear structures. 15 – 21 This technique is efficacious in providing hematoxylin-like contrast in frozen sections and paraffin-embedded blocks and sections. 15 – 21 However, these UV-PARS visualizations lack some essential diagnostic details.…”

“…Previously, PARS has provided complete H&E emulation using a tunable excitation source to independently target the absorption peaks of DNA and cell membrane structures. 17 , 18 While effective in both thin sections and tissue blocks, this technique was largely limited in field of view, resolution, and imaging speed since it required the use of a slow (1 kHz) tunable excitation source. 17 , 18 In this paper, we propose leveraging the optical scattering microscope architecture of the PARS detection system to provide bulk tissue contrast, while using an UV excitation to capture nuclear structures.…”

Non-contact, in-vivo, functional, and structural ophthalmic imaging using multimodal photoacoustic remote sensing (PARS) microscopy and swept source optical coherence tomography (SS-OCT)

“…In addition, the wavelength of PARS excitation beam can be tuned to target a speci c chromophore inside the tissue. The technology has proved its potential over a short period of time in various biomedical applications, such as label-free histological imaging 25,26 , sO 2 mapping and angiogenesis imaging 27 . Very recently, our group (PhotoMedicine Labs) demonstrated non-contact, in-vivo photoacoustic imaging of ocular tissue and vasculature in murine eye for the rst time using PARS microscopy 28 .…”