Page 12 - ITPS-6-2
        P. 12
     INNOSC Theranostics and
            Pharmacological Sciences                                                     Theranostics in neurosurgery
              Theranostics within the surgical resection of brain   for automated analysis of processed images. Depending
            tumors  primarily emphasizes  a  means  to supplement   on the specific disorder and pathology, the capacity to
            surgical resection with the intraoperative diagnosis   train  will  vary.  For example,  pathologies  with  a higher
            of tissue samples. Characteristics granting speed and   prevalence of pathognomonic features will lend themselves
            accuracy have been increasingly explored within the field,   to  greater  ease  in  distinction .  In  a  non-inferiority
                                                                                         [61]
            paving the way for deep learning. Deep learning is a form   randomized  controlled  trial,  Hollon  et al.  assessed  SRH
            of machine learning and artificial intelligence that is giving   paired DCNN to conventional H&E pathological analysis
            way to the development of more diagnostic technology   across 278  cases . Sister samples were generated and
                                                                             [61]
            within automated pathology for neurosurgical resections.   designated to one arm of the trial. The overall diagnostic
            Notably, a step within IOC pertains to the preparation   accuracy was 94.6% for the DCNN arm and 93.9% for
            of  tissue  samples,  which  lends  itself  to  successful  and   the control, suggesting that accuracy is not sacrificed at
            accurate diagnoses. Conventionally, tissue samples   the expense of augmented diagnostic speed. While IOC
            have been processed as frozen sections and subjected to   may consume approximately 20 min in duration, DCNN
            processing and labeling. Processing involves three steps to   is implemented on a nearly real-time scale, as shown in
            ensure the tissue is suitable for fixation within supportive   Figure 3 [62-64] . Further, its potential has been illustrated in
            molds. The steps are: (i) Dehydration with agents such as   other studies that coupled this modality to other forms of
            ethanol or isopropanol, among other alcohols; (ii) clearing,   image preparation, namely, THG microscopy. Hence, the
            involving agents, such as xylene; and (iii) infiltration with   adoption of machine learning within IOC serves utility in
            a medium of choice, such as paraffin [51,52] . The invasiveness   the face of efficiency.
            of these steps may carry downstream consequences  for
            the visualization and analysis of slide samples . These   4.2. THG microscopy
                                                  [53]
            consequences can manifest as structural variations,   As discussed, the processing stage plays a salient role
            including  tissue  shrinkage,  protein  denaturation,  the   in  the  diagnostic  ability  provided  by  machine  learning
            resolution of macromolecules, and the intended degree   and this subset of neurosurgical theranostics. Similar to
            of  staining [54,55] . Conventionally, the processed specimen   SRH, THG is a multiphotonic technique that utilizes a
            is labeled with hematoxylin and eosin (H&E) staining .   label-free application. It uses three photons to produce a
                                                        [56]
            More recently, two techniques have been explored which   single photon with the sum of their energy in a process
            include stimulated Raman histology (SRH) and third   known as photoconversion . The produced images rely
                                                                                     [65]
            harmonic generation (THG) microscopy [57,58] .     on the inherent contrast of the visualized material to
            4.1. SRH                                           create high resolution, bypassing the detriments of certain
                                                               procedures, such as  photobleaching  or reactive oxygen
            SRH, a modality that allows for the analysis of tissue   species (ROS) production [66,67] . A  study of 45  samples
            through an unlabeled and unprocessed method for    assessing THG efficacy in distinguishing gliomas from
            preparation and staining, contributes to the greater   non-tumorous tissue (n = 37 glioma and n = 8 normal)
            preservation of important molecular structures, which   was described by Blokker et al.  According to the study,
                                                                                        [68]
            supports downstream analyses. Developed in 2008, SRH   THG has an imaging capture speed that is 8 times faster
            is an infrared microscopical technique that utilizes the   than SRH, yielding significant advantages regarding speed.
            vibrational frequencies within the chemical bonds of   The researchers applied fully convolutional networks
            proteins, lipids, and DNA; it generates images  highly   (FCN), which is a form of deep learning, based on a set
            reminiscent  of  H&E-produced  imaging [59,60] .  SRH  has   of image-level features determined by three pathologists.
            footholds within spontaneous Raman scattering, which   This was applied to assess the binary diagnostic ability to
            is its original predecessor. This  method, however, is   distinguish between glioma and non-tumor. Overall, the
            multiphotonic and utilizes two lasers to generate the   accuracy was 79% with a mean average precision of 0.83.
            desired  emission  signal  through  stimulated  rather   The results of this study in addition to those of the Hollon
            than spontaneous excitation [59] . Overall, the potent   et al.   corroborate  evidence  for  the  diagnostic  efficacy
                                                                   [61]
            variation  within  the  hydrocarbon  bonds  of  the  sample   of machine learning and artificial intelligence within
            creates ample contrast for quicker image resolution and   IOC while still granting a superior diagnostic speed.
            generation.                                        Nonetheless, development in this field remains relatively
              The capabilities of machine learning in the form of   nascent. The latter of the two studies solely assessed the
            deep convolutional neural networks (DCNNs) have also   diagnosis of gliomas without other intracranial tumors.
            been explored in the context of SRH. DCNNs utilize   The success is extrapolatable to other forms of tumors, such
            trainable features based on histological patterns to allow   as meningiomas and glioblastomas, based on the former
            Volume 6 Issue 2 (2023)                         6                         https://doi.org/10.36922/itps.417
     	
