Patient-specific apparent diffusion maps used to model nutrient availability in degenerated intervertebral discs.

INTRODUCTION: In this study, magnetic resonance imaging data was used to (1) model IVD-specific gradients of glucose, oxygen, lactate, and pH; and (2) investigate possible effects of covariate factors (i.e., disc geometry, and mean apparent diffusion coefficient values) on the IVD's microenvironment. Mathematical modeling of the patient's specific IVD microenvironment could be important when selecting patients for stem cell therapy due to the increased nutrient demand created by that treatment. MATERIALS AND METHODS: Disc geometry and water diffusion coefficients were extracted from MRIs of 37 patients using sagittal T1-weighted images, T2-weighted images, and ADC Maps. A 2-D steady state finite element mathematical model was developed in COMSOL Multiphysics® 5.4 to compute concentration maps of glucose, oxygen, lactate and pH. RESULTS: Concentration of nutrients (i.e., glucose, and oxygen) dropped with increasing distance from the cartilaginous endplates (CEP), whereas acidity levels increased. Most discs experienced poor nutrient levels along with high acidity values in the inner annulus fibrosus (AF). The disc's physiological microenvironment became more deficient as degeneration progressed. For example, minimum glucose concentration in grade 4 dropped by 31.1% compared to grade 3 (p < 0.0001). The model further suggested a strong effect of the following parameters: disc size, AF and CEP diffusivities, metabolic reactions, and cell density on solute concentrations in the disc (p < 0.05). CONCLUSION: The significance of this work implies that the individual morphology and physiological conditions of each disc, even among discs of the same Pfirrmann grade, should be evaluated when modeling IVD solute concentrations.

Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy.

Introduction: Acridine orange (AO) was first extracted from coal tar in the late nineteenth century and was used as a fluorescent dye. In this paper, we review emergent research about novel applications of AO for fluorescence surgery and cancer therapy. Materials and methods: We performed a systematic search in the MEDLINE, PubMed, Cochrane library, Google Scholar, Embase, Web of Science, and Scopus database using combinations of the term "acridine orange" with the following: "surgical oncology," "neuropathology," "microsurgery," "intraoperative fluorescence," "confocal microscopy," "pathology," "endomicroscopy," "guidance," "fluorescence guidance," "oncology," "surgery," "neurooncology," and "photodynamic therapy." Peer-reviewed articles published in English were included in this review. We have also scanned references for relevant articles. Results: We have reviewed studies on the various application of AO in microscopy, endomicroscopy, intraoperative fluorescence guidance, photodynamic therapy, sonodynamic therapy, radiodynamic therapy. Conclusion: Although the number of studies on the clinical use of AO is limited, pilot studies have demonstrated the safety and feasibility of its application as an intraoperative fluorescent dye and as a novel photo- and radio-sensitizator. Further clinical studies are necessary to more definitively assess the clinical benefit AO-based fluorescence guidance, therapy for sarcomas, and to establish feasibility of this new approach for the treatment of other tumor types.

Apparent diffusion coefficient maps in the assessment of surgical patients with lumbar spine degeneration.

PURPOSE: To assess the utility of apparent diffusion coefficient (ADC) maps for the assessment of patients with advanced degenerative lumbar spine disease and describe characteristic features of ADC maps in various degenerative lumbar spinal conditions. METHODS: T1-weighted, T2-weighted and diffusion weighted (DWI) MR images of 100 consecutive patients admitted to the spinal surgery service were assessed. ADC maps were generated from DWI images using Osyrix software. The ADC values and characteristic ADC maps were assessed in the regions of interest over the different pathological entities of the lumbar spine. RESULTS: The study included 452 lumbar vertebral segments available for analysis of ADCs. Characteristic ADC map features were identified for protrusion, extrusion and sequester types of lumbar disk herniations, spondylolisthesis, reactive Modic endplate changes, Pfirrmann grades of IVD degeneration, and compromised spinal nerves. Compromised nerve roots had significantly higher mean ADC values than adjacent (p < 0.001), contralateral (p < 0.001) or adjacent contralateral (p < 0.001) nerve roots. Compared to the normal bone marrow, Modic I changes showed higher ADC values (p = 0.01) and Modic 2 changes showed lower ADC values (p = 0.02) respectively. ADC values correlated with the Pfirrmann grading, however differed from herniated and non-herniated disks of the matched Pfirrmann 3 and 4 grades. CONCLUSION: Quantitative and qualitative evaluation of ADC mapping may provide additional useful information regarding the fluid dynamics of the degenerated spine and may complement standard MRI imaging protocol for the comprehensive assessment of surgical patients with lumbar spine pathology. ADC maps were advantageous in differentiating reactive bone marrow changes, and more precise assessment of the disk degeneration state. ADC mapping of compressed nerve roots showed promise but requires further investigation on a larger cohort of patients.

Intraoperative Fluorescence Imaging for Personalized Brain Tumor Resection: Current State and Future Directions.

INTRODUCTION: Fluorescence-guided surgery is one of the rapidly emerging methods of surgical "theranostics." In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients as well as future applications of recent laboratory and translational studies. METHODS: Review of the literature. RESULTS: A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence-guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-aminolevulinic acid, and indocyanine green), less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine, can be used for rapid tumor detection and pathological tissue examination. Other emerging agents, such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment, are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed. CONCLUSION: We are standing on the threshold of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.