Improving Maximal Safe Brain Tumor Resection with Photoacoustic Remote Sensing Microscopy (2009.10226v1)

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 minutes 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 and 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.

• The paper demonstrates that PARS microscopy yields real-time, high-resolution histological images for precise brain tumor resection.
• The technique replicates H&E staining by targeting optical absorption of DNA and cytoplasmic components in a contact-free format.
• Validation shows the method scans a 1 mm² area in under 1.5 minutes, significantly improving intraoperative tissue differentiation.

Advancements in Brain Tumor Resection Using Photoacoustic Remote Sensing Microscopy

The paper "Improving Maximal Safe Brain Tumor Resection with Photoacoustic Remote Sensing Microscopy" introduces a novel imaging technique aimed at enhancing the surgical removal of brain tumors. The proposed method, photoacoustic remote sensing (PARS) microscopy, is an all-optical, non-contact, and label-free imaging system designed to emulate the histopathological contrast of standard H&E stained slides. The scientific team has developed a method enabling real-time, high-resolution imaging of unstained brain tissues, potentially improving the precision of intraoperative guidance during brain tumor surgeries.

Motivation and Challenges

Malignant brain tumors, particularly gliomas, present one of the most significant clinical challenges due to their poor prognosis and the criticality of the surrounding brain tissue. Achieving a maximal extent of resection without compromising neurological function is key to improving patient outcomes. Existing techniques such as MRI and frozen section histopathology have limitations in speed and accuracy, prompting the exploration of new methods for intraoperative assessment.

Photoacoustic Remote Sensing Microscopy

PARS utilizes the endogenous contrast of tissues by targeting the optical absorption peaks of DNA and cytoplasmic components, simulating traditional H&E staining without the need for dyes. The system operates in a reflection-mode format, overcoming limitations of previous contact-based techniques that are unsuitable for the neurosurgical environment. The PARS system achieves this through a combination of a 266 nm fast excitation source and a tunable excitation laser, producing multiwavelength images with contrast analogous to hematoxylin and eosin staining.

Results and Empirical Validation

The implementation of PARS demonstrated the capability to produce detailed histological imagery in real-time, achieving spatial resolutions of approximately 2.5 μm using a single UV wavelength and down to sub-micron levels with multiwavelength acquisitions. A 1 mm by 1 mm area could be scanned in under 1.5 minutes, with further advancements promising significant improvements in speed and FOV coverage. Comparative analyses with traditional histopathological slides confirm the reliability of PARS in distinguishing between necrotic and viable tissue, solid tumor margins, and other clinically relevant features, such as the identification of oligodendrocytes.

Implications and Future Directions

PARS microscopy presents several promising implications for both clinical and research contexts. The in-situ imaging capability of this system could vastly improve the precision of surgical resection of gliomas, reducing the likelihood of remnant malignant tissue and thus improving overall survival rates. Furthermore, since PARS images maintain a similar appearance to H&E slides, the adoption in clinical settings minimizes the necessity for retraining pathologists.

In future developments, the research team aims to increase the imaging speed and resolution further by incorporating advanced laser technologies. Additionally, extending the wavelength range could enhance biomolecular contrast, critical for comprehensive tissue differentiation. Another potential advancement includes adapting the system for volumetric imaging to better accommodate resected tissues.

Conclusion

This paper represents a significant step toward the realization of a real-time, label-free pathological assessment method during neurosurgery. The results corroborate the utility of PARS for rapidly obtaining histological-like images which are indicative of their potential widespread application in neurosurgical intervention. The ongoing enhancements to imaging speed and contrast targeting make PARS a promising technology for future integration into operating rooms, with significant potential to revolutionize the intraoperative decision-making process in neurosurgery.