Browsing by Author "Mihaylov, Plamen V."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Comparison of Artificial Intelligence and Eyeball Method in the Detection of Fatty Liver Disease
    (2023-07-26) Catron, Evan J.; Passarelli, Robert P.; Danielle, Wilmes; Wei, Barry; Le, Thi M.U.; Li, Ping; Zhang, Wenjun; Lin, Jingmei; Melcher, Mark L.; Mihaylov, Plamen V.; Kubal, Chandrashekhar A.; Mangus, Robert S.; Ekser, Burcin
    Background: Quantification of liver fat content relies on visual microscopic inspection of liver biopsies by pathologists. Their percent macrosteatosis (%MaS) estimation is vital in determining donor liver transplantability; however, the eyeball method may vary between observers. Overestimations of %MaS can potentially lead to the discard of viable donor livers. We hypothesize that artificial intelligence (AI) could be helpful in providing a more objective and accurate measurement of %MaS. Methods: Literature review identified HALO (image analysis) and U-Net (deep-learning) as high-accuracy AI programs capable of calculating %MaS in liver biopsies. We compared (i) an experienced pathologist’s and (ii) a transplant surgeon’s eyeball %MaS estimations from de-novo liver transplant (LT) biopsy samples taken 2h post-reperfusion to (iii) the HALO-calculated %MaS (Fig.1). 250 patients had undergone LT at Indiana University between 2020-2021, and 211 had sufficient data for inclusion. Each biopsy was digitized into 5 random non-overlapping tiles at 20x magnification (a total of 1,055 images). We used HALO software for analysis and set the minimum vacuole area to 10μm² to avoid the inclusion of microsteatosis. Microsteatosis was excluded by the pathologist and the surgeon by the eyeball method using the same 1,055 images. Each %MaS estimation was compared with early allograft dysfunction (EAD). EAD is defined by the presence of at least one of the following: INR >1.6 on postoperative day (POD) 7, total bilirubin >10mg/dL on POD7, or AST/ALT >2000IU/L within the first 7 days following LT. Results: Of 211 LTs, 42 (19.9%) had EAD. The mean %MaS estimation of pathologist and transplant surgeon were 6.3% (SD: 11.9%) and 3.2% (SD: 6.4%), respectively. HALO yielded a significantly lower mean %MaS of 2.6% (SD: 2.6%) than the pathologist’s eyeball method (p<0.001). The mean %MaS calculated by HALO was higher in EAD patients than in non-EAD (p=0.032), but this difference did not reach statistical significance in the pathologist’s estimation (p=0.069). Conclusions: Although mean %MaS measurements from all parties were mild (<10%), human eyeball estimations of %MaS were significantly higher than HALO’s %MaS. The HALO-calculated %MaS differed significantly between the EAD and non-EAD LTs which might suggest a possible correlation between the AI’s steatosis analysis and EAD outcomes. However, pathologic variables other than %MaS (necrosis or cholestasis) should be included in future analyses to determine whether %MaS is the dominant parameter predicting EAD. AI is a promising tool to quantify liver steatosis and will help pathologists and transplant surgeons predict liver transplant viability.
  • Thumbnail Image
    Item
    Human organ donor-derived vagus nerve biopsies allow for well-preserved ultrastructure and high-resolution mapping of myelinated and unmyelinated fibers
    (Springer Nature, 2021) Havton, Leif A.; Biscola, Natalia P.; Stern, Esther; Mihaylov, Plamen V.; Kubal, Chandrashekhar A.; Wo, John M.; Gupta, Anita; Baronowsky, Elizabeth; Ward, Matthew P.; Jaffey, Deborah M.; Powley, Terry L.; Surgery, School of Medicine
    The vagus nerve provides motor, sensory, and autonomic innervation of multiple organs, and electrical vagus nerve stimulation (VNS) provides an adjunctive treatment option for e.g. medication-refractory epilepsy and treatment-resistant depression. The mechanisms of action for VNS are not known, and high-resolution anatomical mapping of the human vagus nerve is needed to better understand its functional organization. Electron microscopy (EM) is required for the detection of both myelinated and unmyelinated axons, but access to well-preserved human vagus nerves for ultrastructural studies is sparse. Intact human vagus nerve samples were procured intra-operatively from deceased organ donors, and tissues were immediately immersion fixed and processed for EM. Ultrastructural studies of cervical and sub-diaphragmatic vagus nerve segments showed excellent preservation of the lamellated wall of myelin sheaths, and the axolemma of myelinated and unmyelinated fibers were intact. Microtubules, neurofilaments, and mitochondria were readily identified in the axoplasm, and the ultrastructural integrity of Schwann cell nuclei, Remak bundles, and basal lamina was also well preserved. Digital segmentation of myelinated and unmyelinated axons allowed for determination of fiber size and myelination. We propose a novel source of human vagus nerve tissues for detailed ultrastructural studies and mapping to support efforts to refine neuromodulation strategies, including VNS.
  • Thumbnail Image
    Item
    Laterality, sexual dimorphism, and human vagal projectome heterogeneity shape neuromodulation to vagus nerve stimulation
    (Springer Nature, 2024-11-19) Biscola, Natalia P.; Bartmeyer, Petra M.; Beshay, Youssef; Stern, Esther; Mihaylov, Plamen V.; Powley, Terry L.; Ward, Matthew P.; Havton, Leif A.; Surgery, School of Medicine
    Neuromodulation by vagus nerve stimulation (VNS) provides therapeutic benefits in multiple medical conditions, including epilepsy and clinical depression, but underlying mechanisms of action are not well understood. Cervical vagus nerve biopsies were procured from transplant organ donors for high resolution light microscopy (LM) and transmission electron microscopy (TEM) to map the human fascicular and sub-fascicular organization. Cervical vagal segments show laterality with right sided dominance in fascicle numbers and cross-sectional areas as well as sexual dimorphism with female dominance in fascicle numbers. The novel and unprecedented detection of numerous small fascicles by high resolution LM and TEM expand the known fascicle size range and morphological diversity of the human vagus nerve. Ground truth TEM quantification of all myelinated and unmyelinated axons within individual nerve fascicles show marked sub-fascicular heterogeneity of nerve fiber numbers, size, and myelination. A heuristic action potential interpreter (HAPI) tool predicts VNS-evoked compound nerve action potentials (CNAPs) generated by myelinated and unmyelinated nerve fibers and validates functional dissimilarity between fascicles. Our findings of laterality, sexual dimorphism, and an expanded range of fascicle size heterogeneity provide mechanistic insights into the varied therapeutic responses and off-target effects to VNS and may guide new refinement strategies for neuromodulation.