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Browsing by Author "Kani, Yukitaka"

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    Biocompatibility of the fiberoptic microneedle device chronically implanted in the rat brain
    Kani, Yukitaka; Hinckley, Jonathan; Robertson, John L.; Mehta, Jason M.; Rylander, Christopher G.; Rossmeisl, John H. Jr. (Elsevier, 2022-03)
    The fiberoptic microneedle device (FMD) is a fused-silica microcatheter capable of co-delivery of fluids and light that has been developed for convection-enhanced delivery and photothermal treatments of glioblastoma. Here we investigate the biocompatibility of FMD fragments chronically implanted in the rat brain in the context of evaluating potential mechanical device failure. Fischer rats underwent craniectomy procedures for sham control (n & nbsp;= 16) or FMD implantation (n = 16) within the brain. Rats were examined daily after implantation, and at 14, 30, 90, and 180 days after implantation were evaluated via computed tomography of the head, hematologic and blood biochemical profiling, and necropsy examinations. Clinical signs of illness and distant implant migration were not observed, and blood analyses were not different between control and FMD implanted groups at any time. Mild inflammatory and astrogliotic reactions localized to the treatment sites within the brain were observed in all groups, more robust in FMD implanted groups compared to controls at days 30 and 90, and decreased in severity over days 90-180 of the study. One rat developed a chronic, superficial surgical site pyogranuloma attributed to the FMD silica implant. Chronically implanted FMD fragments were well tolerated clinically and resulted in anticipated mild, localized brain tissue responses that were comparable with other implanted biomaterials in the brain.
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    Comparison of direct measurement of intracranial pressures and presumptive clinical and magnetic resonance imaging indicators of intracranial hypertension in dogs with brain tumors
    Giannasi, Savannah; Kani, Yukitaka; Hsu, Fang-Chi; Rossmeisl, John H. Jr. (2020-05-16)
    Background Intracranial hypertension (ICH) is often presumptively diagnosed based on clinical or imaging findings. Clinical or imaging surrogates of ICH are not usually validated with reference standard direct intracranial pressure (dICP) recordings. Hypotheses Dogs with brain magnetic resonance imaging (MRI) or clinical features of presumed ICH would have higher dICP than dogs lacking those features. Animals Twenty dogs with gliomas and 3 normal controls. Methods Prospective, convenience study. Dogs were presumptively categorized with normal ICP or ICH from scores generated from described clinical and brain MRI indicators of ICH. dICP was recorded in anesthetized dogs using an intraparenchymal microsensor and compared between groups. Results dICP was not different between control (10.4 +/- 2.1 mm Hg) and dogs with glioma (15.6 +/- 8.3 mm Hg), or between dogs in clinically predicted ICP groups. Compared with dogs with MRI-predicted normal ICP, MRI-predicted ICH dogs had higher dICP (10.3 +/- 4.1 versus 19.2 +/- 7.9 mm Hg, P = .004), larger tumors (1.45 +/- 1.2 versus 5.71 +/- 3.03 cm(3), P = .0004), larger optic nerve sheath diameters, and 14/14 (100%) displayed structural anatomical shifts on MRI. At a dICP threshold of 15 mm Hg, the sensitivity of MRI for predicting ICH was 90% and the specificity 69%. Conclusions and Clinical Relevance dICP measurements are feasible in dogs with brain tumors. MRI features including brain herniations, mass effect, and optic nerve size aid in the identification of dogs with ICH. Clinical estimation of ICP did not discriminate between dogs with and without ICH.
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    Diagnostic accuracy of stereotactic brain biopsy for intracranial neoplasia in dogs: Comparison of biopsy, surgical resection, and necropsy specimens
    Kani, Yukitaka; Cecere, Thomas E.; Lahmers, Kevin K.; LeRoith, Tanya; Zimmerman, Kurt L.; Isom, Scott; Hsu, Fang-Chi; Debinski, Waldemar; Robertson, John L.; Rossmeisl, John H. Jr. (American College of Veterinary Internal Medicine, 2019-05)
    Background Stereotactic brain biopsy (SBB) is a technique that allows for definitive diagnosis of brain lesions. Little information is available regarding the diagnostic utility of SBB in dogs with intracranial diseases. Objective To investigate the diagnostic accuracy (DA) of SBB in dogs with brain tumors. Animals Thirty-one client-owned dogs that underwent SBB followed by surgical resection or necropsy examinations. Methods Retrospective observational study. Two pathologists blinded to SBB and reference standard diagnoses reviewed histologic specimens and typed and graded tumors according to World Health Organization and revised canine glioma classification criteria. Agreement between tumor type and grade from SBB were compared to reference standards and assessed using kappa statistics. Patient and technical factors associated with agreement also were examined. Results Stereotactic brain biopsy specimens were obtained from 24 dogs with gliomas and 7 with meningiomas. Tumor type agreement between SBB and the reference standard was observed in 30/31 cases (kappa = 0.95). Diagnostic concordance was perfect for meningiomas. Grade agreement among gliomas was observed in 18/23 cases (kappa = 0.47). Stereotactic brain biopsy underrepresented the reference standard glioma grade in cases with disagreement. The DA of SBB was 81%, with agreement noted in 56/69 biopsy samples. Smaller tumors and fewer SBB specimens obtained were significantly associated with diagnostic discordance. Conclusions and Clinical Importance The DA of SBB readily allows for the diagnosis of common brain tumors in dogs. Although glioma grade discordance was frequent, diagnoses obtained from SBB are sufficient to currently inform therapeutic decisions. Multiple SBB specimens should be collected to maximize DA.
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    High-Frequency Irreversible Electroporation (H-FIRE) Induced Blood-Brain Barrier Disruption Is Mediated by Cytoskeletal Remodeling and Changes in Tight Junction Protein Regulation
    Partridge, Brittanie R.; Kani, Yukitaka; Lorenzo, Melvin F.; Campelo, Sabrina N.; Allen, Irving C.; Hinckley, Jonathan; Hsu, Fang-Chi; Verbridge, Scott S.; Robertson, John L.; Davalos, Rafael V.; Rossmeisl, John H. Jr. (MDPI, 2022-06-11)
    Glioblastoma is the deadliest malignant brain tumor. Its location behind the blood–brain barrier (BBB) presents a therapeutic challenge by preventing effective delivery of most chemotherapeutics. H-FIRE is a novel tumor ablation method that transiently disrupts the BBB through currently unknown mechanisms. We hypothesized that H-FIRE mediated BBB disruption (BBBD) occurs via cytoskeletal remodeling and alterations in tight junction (TJ) protein regulation. Intracranial H-FIRE was delivered to Fischer rats prior to sacrifice at 1-, 24-, 48-, 72-, and 96 h post-treatment. Cytoskeletal proteins and native and ubiquitinated TJ proteins (TJP) were evaluated using immunoprecipitation, Western blotting, and gene-expression arrays on treated and sham control brain lysates. Cytoskeletal and TJ protein expression were further evaluated with immunofluorescent microscopy. A decrease in the F/G-actin ratio, decreased TJP concentrations, and increased ubiquitination of TJP were observed 1–48 h post-H-FIRE compared to sham controls. By 72–96 h, cytoskeletal and TJP expression recovered to pretreatment levels, temporally corresponding with increased claudin-5 and zonula occludens-1 gene expression. Ingenuity pathway analysis revealed significant dysregulation of claudin genes, centered around claudin-6 in H-FIRE treated rats. In conclusion, H-FIRE is capable of permeating the BBB in a spatiotemporal manner via cytoskeletal-mediated TJP modulation. This minimally invasive technology presents with applications for localized and long-lived enhanced intracranial drug delivery.
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    Risk factors for adverse events occurring after recovery from stereotactic brain biopsy in dogs with primary intracranial neoplasia
    Shinn, Richard L.; Kani, Yukitaka; Hsu, Fang-Chi; Rossmeisl, John H. Jr. (2020-09-14)
    Background Stereotactic brain biopsy (SBB) allows for histopathologic diagnosis of brain tumors. Adverse events (AE) occur in 5 to 29% of dogs after SBB, but risk factors associated with developing AE are poorly described. Objective Identify clinicopathologic, diagnostic imaging, or procedural variables that are associated with AE in dogs after SBB. Animals Twenty-nine dogs with brain tumors. Methods Retrospective, case-control study. Dogs had laboratory investigations performed before SBB, as well as clinical examinations and diagnostic imaging of the brain before and after SBB. Cases experienced AE after SBB including transient exacerbation of preexisting neurologic deficits, transient new deficits, or permanent neurologic deficits. Controls had SBB performed without AE. Fisher's exact and Student'sttests were used to examine associations between the postulated risk factors and AE. Results Adverse events occurred in 8/29 (27%) dogs, and 7/8 AE (88%) were transient. Cases were significantly more likely to have T2W-heterogenous tumors (88 versus 38%;P= .04) and lower platelet counts (194.75 +/- 108.32 versus 284.29 +/- 68.54 x10(3)/mm(3),P= .006). Dogs with gradient echo signal voids present on baseline imaging were significantly more likely to have hemorrhage present after biopsy, and 7/8 (88%) of cases had hemorrhage on imaging after SBB. Conclusion and Clinical Importance Twenty-seven percent of dogs undergoing SBB experience AE, with the majority of AE resolving with 1 week. Platelet counts should be >= 185 000/mm(3)to minimize risk of SBB-associated AE. Observation of intracranial hemorrhage after biopsy can have important clinical implications, as this was observed in 88% of dogs with AE.
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    Temporal Characterization of Blood–Brain Barrier Disruption with High-Frequency Electroporation
    Lorenzo, Melvin F.; Thomas, Sean C.; Kani, Yukitaka; Hinckley, Jonathan; Lee, Matthew; Adler, Joy; Verbridge, Scott S.; Hsu, Fang-Chi; Robertson, John L.; Davalos, Rafael V.; Rossmeisl, John H. Jr. (MDPI, 2019-11-23)
    Treatment of intracranial disorders suffers from the inability to accumulate therapeutic drug concentrations due to protection from the blood–brain barrier (BBB). Electroporation-based therapies have demonstrated the capability of permeating the BBB, but knowledge of the longevity of BBB disruption (BBBD) is limited. In this study, we quantify the temporal, high-frequency electroporation (HFE)-mediated BBBD in an in vivo healthy rat brain model. 40 male Fisher rats underwent HFE treatment; two blunt tipped monopolar electrodes were advanced into the brain and 200 bursts of HFE were delivered at a voltage-to-distance ratio of 600 V/cm. BBBD was verified with contrast enhanced T1W MRI (gadopentetate dimeglumine) and pathologically (Evans blue dye) at time points of 1, 24, 48, 72, and 96 h after HFE. Contrast enhanced T1W scans demonstrated BBBD for 1 to 72 h after HFE but intact BBB at 96 h. Histologically, tissue damage was restricted to electrode insertion tracks. BBBD was induced with minimal muscle contractions and minimal cell death attributed to HFE. Numerical modeling indicated that brief BBBD was induced with low magnitude electric fields, and BBBD duration increased with field strength. These data suggest the spatiotemporal characteristics of HFE-mediated BBBD may be modulated with the locally applied electric field.