Publications by authors named "Todd Hollon"

Article Synopsis
  • Accurate intraoperative diagnosis of primary CNS lymphoma (PCNSL) is vital for surgical decisions but is challenging due to similar features with other CNS diseases; a new method combines stimulated Raman histology (SRH) with deep learning to improve this process.
  • The RapidLymphoma system uses a portable Raman microscope to create virtual images of tissue samples in under three minutes and employs a deep learning model trained on 54,000 images, allowing it to detect PCNSL and differentiate it from other conditions effectively.
  • In testing, RapidLymphoma achieved a high accuracy rate of 97.81%, performing better than traditional methods, and demonstrated its capability to identify specific histological features crucial for diagnosis, providing quick feedback
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A critical challenge in glioma treatment is detecting tumour infiltration during surgery to achieve safe maximal resection. Unfortunately, safely resectable residual tumour is found in the majority of patients with glioma after surgery, causing early recurrence and decreased survival. Here we present FastGlioma, a visual foundation model for fast (<10 s) and accurate detection of glioma infiltration in fresh, unprocessed surgical tissue.

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Volumetric biomedical microscopy has the potential to increase the diagnostic information extracted from clinical tissue specimens and improve the diagnostic accuracy of both human pathologists and computational pathology models. Unfortunately, barriers to integrating 3-dimensional (3D) volumetric microscopy into clinical medicine include long imaging times, poor depth/z-axis resolution, and an insufficient amount of high-quality volumetric data. Leveraging the abundance of high-resolution 2D microscopy data, we introduce masked slice diffusion for super-resolution (MSDSR), which exploits the inherent equivalence in the data-generating distribution across all spatial dimensions of biological specimens.

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Article Synopsis
  • Accurate intraoperative diagnosis of primary CNS lymphoma (PCNSL) is challenging due to overlapping features with other CNS conditions, but a new method combining stimulated Raman histology (SRH) and deep learning seeks to improve this.
  • The deep learning system, RapidLymphoma, analyzes unprocessed tissue samples quickly, achieving high accuracy in distinguishing PCNSL from other entities, with an overall accuracy of 97.81% in a test cohort.
  • RapidLymphoma not only provides rapid diagnostic results but also visual feedback, aiding surgical decision-making and potential treatment strategies within a critical timeframe.
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The most widely used fluorophore in glioma-resection surgery, 5-aminolevulinic acid (5-ALA), is thought to cause the selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumour cells. Here we show that the clinical detection of PpIX can be improved via a microscope that performs paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF). We validated the technique in fresh tumour specimens from 115 patients with high-grade gliomas across four medical institutions.

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Objective: Achieving appropriate spinopelvic alignment has been shown to be associated with improved clinical symptoms. However, measurement of spinopelvic radiographic parameters is time-intensive and interobserver reliability is a concern. Automated measurement tools have the promise of rapid and consistent measurements, but existing tools are still limited to some degree by manual user-entry requirements.

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Article Synopsis
  • This study focuses on a clinical trial exploring the use of adenoviral vectors to enhance immune responses in patients with high-grade gliomas, which are aggressive brain tumors with poor treatment outcomes.
  • The trial involved administering two specific vectors (HSV1-TK and Flt3L) into the tumor site of treatment-naive adults, using a dose-finding approach to evaluate safety and potential effectiveness.
  • Conducted at the University of Michigan, the study aimed to assess how these vectors could stimulate anti-tumor immunity and improve patient prognosis after standard treatment protocols.
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Learning high-quality, self-supervised, visual representations is essential to advance the role of computer vision in biomedical microscopy and clinical medicine. Previous work has focused on self-supervised representation learning (SSL) methods developed for instance discrimination and applied them directly to image patches, or fields-of-view, sampled from gigapixel whole-slide images (WSIs) used for cancer diagnosis. However, this strategy is limited because it (1) assumes patches from the same patient are independent, (2) neglects the patient-slide-patch hierarchy of clinical biomedical microscopy, and (3) requires strong data augmentations that can degrade downstream performance.

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The AI era in medicine has ushered in new opportunities to improve the diagnosis and treatment of human disease. CHARM, an AI algorithm described in this issue, has the potential to streamline molecular classification, intraoperative diagnosis, surgical decision making, and trial enrollment for glioma patients.

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Accurate intraoperative diagnosis is essential for providing safe and effective care during brain tumor surgery. Our standard-of-care diagnostic methods are time, resource, and labor intensive, which restricts access to optimal surgical treatments. To address these limitations, we propose an alternative workflow that combines stimulated Raman histology (SRH), a rapid optical imaging method, with deep learning-based automated interpretation of SRH images for intraoperative brain tumor diagnosis and real-time surgical decision support.

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Background: Guidelines for determining shunt dependence after aneurysmal subarachnoid hemorrhage (aSAH) remain unclear. We previously demonstrated change in ventricular volume (VV) between head CT scans taken pre- and post-EVD clamping was predictive of shunt dependence in aSAH. We sought to compare the predictive value of this measure to more commonly used linear indices.

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Molecular classification has transformed the management of brain tumors by enabling more accurate prognostication and personalized treatment. However, timely molecular diagnostic testing for patients with brain tumors is limited, complicating surgical and adjuvant treatment and obstructing clinical trial enrollment. In this study, we developed DeepGlioma, a rapid (<90 seconds), artificial-intelligence-based diagnostic screening system to streamline the molecular diagnosis of diffuse gliomas.

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Development of spatial-integrative pre-clinical models is needed for glioblastoma, which are heterogenous tumors with poor prognosis. Here, we present an optimized protocol to generate three-dimensional ex vivo explant slice glioma model from orthotopic tumors, genetically engineered mouse models, and fresh patient-derived specimens. We describe a step-by-step workflow for tissue acquisition, dissection, and sectioning of 300-μm tumor slices maintaining cell viability.

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Article Synopsis
  • Molecular classification has improved brain tumor management by facilitating personalized treatment and accurate prognoses, but access to timely diagnostics remains a challenge.
  • The study utilizes stimulated Raman histology combined with deep learning to predict molecular features critical for glioma categorization, achieving high accuracy in real-time settings.
  • The DeepGlioma system demonstrated a classification accuracy of 93.2% in a surgical context and significantly outperformed traditional methods, showcasing its potential as a rapid diagnostic tool for brain tumors.
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Purpose: Glioblastoma(GBM) is a lethal disease characterized by inevitable recurrence. Here we investigate the molecular pathways mediating resistance, with the goal of identifying novel therapeutic opportunities.

Experimental Design: We developed a longitudinal in vivo recurrence model utilizing patient-derived explants to produce paired specimens(pre- and post-recurrence) following temozolomide(TMZ) and radiation(IR).

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Article Synopsis
  • Federated learning (FL) allows for developing machine learning models in health care without needing to share sensitive data, overcome challenges associated with conventional data aggregation.
  • A multicenter study involving five neurosurgery departments aimed to train a convolutional neural network for detecting intracranial hemorrhage (ICH) using FL, achieving an area under the ROC curve of 0.9487.
  • The results showed that while the FL model performed slightly worse than a centrally trained model, it proved to be more generalizable and opened new opportunities for collaboration in neurosurgical research.
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Giant cell tumors of bone (GCTBs) are benign osteolytic neoplasms that can be treated with either gross-total resection or subtotal resection with adjuvant radiotherapy. For the rare GCTB of the temporal bone, close proximity to critical structures can produce functional deficits and make gross-total resection difficult to achieve without significant morbidity. We present the case of a 28-year-old woman with progressive facial paresis, otalgia, neck pain, imbalance, and subjective hearing loss.

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Purpose: The estimated incidence of pituitary adenomas in the general population is 10-30%, yet radiographic diagnosis remains a challenge. Diagnosis is complicated by the heterogeneity of radiographic features in both normal (e.g.

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Intra-tumoral heterogeneity is a hallmark of glioblastoma that challenges treatment efficacy. However, the mechanisms that set up tumor heterogeneity and tumor cell migration remain poorly understood. Herein, we present a comprehensive spatiotemporal study that aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties and a specific, actionable, spatial transcriptomic signature.

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Surgery is the first-line therapy for most benign and malignant skull base tumors. Extent of resection (EOR) is a metric commonly used for preoperative surgical planning and to predict risk of postoperative tumor recurrence. Therefore, understanding the evidence on EOR in skull base neurosurgery is essential to providing optimal care for each patient.

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Background: Accurate specimen analysis of skull base tumors is essential for providing personalized surgical treatment strategies. Intraoperative specimen interpretation can be challenging because of the wide range of skull base pathologies and lack of intraoperative pathology resources.

Objective: To develop an independent and parallel intraoperative workflow that can provide rapid and accurate skull base tumor specimen analysis using label-free optical imaging and artificial intelligence.

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Although rare, intramedullary spinal cavernous malformations have a 1.4%-6.8% annual hemorrhage risk and can cause significant morbidity.

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Background And Importance: There is no consensus on the optimal surgical approach for managing optic nerve gliomas. For solely intraorbital tumors, a single-stage lateral orbitotomy approach for resection may be performed, but when the nerve within the optic canal is affected, two-stage cranial and orbital approaches are often used. The authors describe their technique to safely achieve aggressive nerve resection to minimize the probability of recurrence that might affect the optic tracts, optic chiasm, and contralateral optic nerve.

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Background And Introduction: Dural arteriovenous fistulas (dAVFs) are a rare pathology with a clinical presentation related to their anatomical location. Craniocervical junction (CCJ) dAVFs are challenging to treat given the delicate structures that surround the CCJ. Endovascular treatment has evolved significantly in the past decade, but open microsurgery remains an invaluable tool for this pathology.

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