Browsing by Author "Daniel, Gregory B."
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- Characterizing the Ablative Effects of Histotripsy for Osteosarcoma: In Vivo Study in DogsRuger, Lauren N.; Hay, Alayna N.; Vickers, Elliana R.; Coutermarsh-Ott, Sheryl; Gannon, Jessica M.; Covell, Hannah S.; Daniel, Gregory B.; Laeseke, Paul F.; Ziemlewicz, Timothy J.; Kierski, Katharine R.; Ciepluch, Brittany J.; Vlaisavljevich, Eli; Tuohy, Joanne L. (MDPI, 2023-01-25)Osteosarcoma (OS) is a malignant bone tumor treated by limb amputation or limb salvage surgeries and chemotherapy. Histotripsy is a non-thermal, non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue. Recent ex vivo and in vivo pilot studies have demonstrated the ability of histotripsy for ablating OS but were limited in scope. This study expands on these initial findings to more fully characterize the effects of histotripsy for bone tumors, particularly in tumors with different compositions. A prototype 500 kHz histotripsy system was used to treat ten dogs with suspected OS at an intermediate treatment dose of 1000 pulses per location. One day after histotripsy, treated tumors were resected via limb amputation, and radiologic and histopathologic analyses were conducted to determine the effects of histotripsy for each patient. The results of this study demonstrated that histotripsy ablation is safe and feasible in canine patients with spontaneous OS, while offering new insights into the characteristics of the achieved ablation zone. More extensive tissue destruction was observed after histotripsy compared to that in previous reports, and radiographic changes in tumor size and contrast uptake following histotripsy were reported for the first time. Overall, this study significantly expands our understanding of histotripsy bone tumor ablation and informs future studies for this application.
- Comparison of linear and volumetric criteria for the determination of therapeutic response in dogs with intracranial gliomasGarcia Mora, Josefa Karina; Robertson, John L.; Hsu, Fang-Chi; Shinn, Richard Levon; Larson, Martha M.; Rylander, Christopher G.; Whitlow, Christopher T.; Debinski, Waldemar; Davalos, Rafael V.; Daniel, Gregory B.; Rossmeisl, John H. Jr. (Wiley, 2022-05)Background: Brain tumor therapeutic responses can be quantified from magnetic resonance images (MRI) using 1- (1D) and 2-dimensional (2D) linear and volumetric methods, but few studies in dogs compare these techniques. Hypotheses: Linear methods will be obtained faster, but have less agreement than volumetric measurements. Therapeutic response agreement will be highest with the total T2W tumor volumetric (TTV) method. Therapeutic response at 6-weeks will correlate with overall survival (OS). Animals: Forty-six dogs with intracranial gliomas. Methods: Prospective study. Three raters measured tumors using 1D and 2D linear, TTV, and contrast-enhancing volumetric (CEV) techniques on 143 brain MRI to determine agreement between methods, define therapeutic responses, and assess relations with OS. Results: Raters performed 1D the fastest (2.9 ± 0.57 minutes) and CEV slowest (17.8 ± 6.2 minutes). Inter- and intraobserver agreements were excellent (intraclass correlations ≥.91) across methods. Correlations between linear (1D vs 2D; ρ >.91) and volumetric (TTV vs CEV; ρ >.73) methods were stronger than linear to volumetric comparisons (ρ range,.26-.59). Incorporating clinical and imaging data resulted in fewer discordant therapeutic responses across methods. Dogs having partial tumor responses at 6 weeks had a lower death hazard than dogs with stable or progressive disease when assessed using 2D, CEV, and TTV (hazard ration 2.1; 95% confidence interval, 1.22-3.63; P =.008). Conclusions and Clinical Importance: One-dimensional, 2D, CEV, and TTV are comparable for determining therapeutic response. Given the simplicity, universal applicability, and superior performance of the TTV, we recommend its use to standardize glioma therapeutic response criteria.
- Evaluation of Thyroid to Background Ratios in Hyperthyroid CatsBettencourt, Ann Elizabeth (Virginia Tech, 2014-07-17)Hyperthyroidism is the most common feline endocrinopathy. 131I is the treatment of choice, and over 50,000 cats have been treated using an empirical fixed dose. Better treatment responses could be achieved by tailoring the dose based on the severity of disease. Scintigraphy is the best method to quantify the severity of the disease. Previously established scintigraphic quantitative methods, thyroid to salivary ratio (T:S ratio) and % dose uptake, are the most widely recognized measurements. Recently, the thyroid to background ratio (T:B ratio) has been proposed as an alternate method to assess function and predict 131I treatment response. The purpose of this study was to determine the best location of a background ROI, which should be reflective of blood pool activity. We also hypothesized that the T:B ratio using the determined background ROI would provide improved correlation to T4 when compared to T:S ratio and % dose uptake in hyperthyroid cats. Fifty-six hyperthyroid cats were enrolled. T4 was used as the standard measure of thyroid function and was obtained prior to thyroid scintigraphy and 131I therapy. Blood samples were collected at the time of scintigraphy and radioactivity within the sample was measured. The plasma radioactivity was compared to the background ROI count densities in 8 anatomic regions using linear regression analysis for 55 cats. One cat was excluded from the study because of an injection error during scintigraphy. T:B and T:S ratios, and % dose uptake on scintigraphy were then compared to serum T4 by linear regression analysis for 39 cats. Sixteen cats were excluded because of recent methimazole or Y/D diet use, or incomplete data. The heart ROI correlated best to plasma pertechnetate activity (r = 0.70). % dose uptake correlated best to serum T4 (r = 0.74), followed by T:S ratio (r = 0.66), followed by the T:B ratio using the heart ROI (r = 0.59). Placing an ROI over the heart is the best method of quantifying plasma radioactivity. T:B ratio using the heart ROI as the background is a good predictor T4 but percent dose uptake and T:S ratio proved to be better predictors of T4 than any of the T:B ratios. Therefore, our hypothesis was not supported. The T:B ratio may not provide the best scintigraphic measurement of thyroid function. Hence it is unlikely to accurately predict treatment response to 131I therapy.
- Histotripsy Ablation of Spontaneously Occurring Canine Bone TumorsRuger, Lauren N.; Hay, Alayna N.; Gannon, Jessica M.; Sheppard, Hannah O.; Coutermarsh-Ott, Sheryl L.; Daniel, Gregory B.; Kierski, Katharine R.; Ciepluch, Brittany J.; Vlaisavljevich, Eli; Tuohy, Joanne L. (IEEE, 2023-01)Objective: Osteosarcoma (OS) is a devastating primary bone tumor in dogs and humans with limited non-surgical treatment options. As the first completely non-invasive and non-thermal ablation technique, histotripsy has the potential to significantly improve the standard of care for patients with primary bone tumors. Introduction: Standard of care treatment for primary appendicular OS involves surgical resection via either limb amputation or limb-salvage surgery for suitable candidates. Biological similarities between canine and human OS make the dog an informative comparative oncology research model to advance treatment options for primary OS. Evaluating histotripsy for ablating spontaneous canine primary OS will build a foundation upon which histotripsy can be translated clinically into a standard of care therapy for canine and human OS. Methods: Five dogs with suspected spontaneous OS were treated with a 500 kHz histotripsy system guided by real-time ultrasound image guidance. Spherical ablation volumes within each tumor (1.25-3 cm in diameter) were treated with single cycle histotripsy pulses applied at a pulse repetition frequency of 500 Hz and a dose of 500 pulses/point. Results: Tumor ablation was successfully identified grossly and histologically within the targeted treatment regions of all subjects. Histotripsy treatments were well-tolerated amongst all patients with no significant clinical adverse effects. Conclusion & Significance: Histotripsy safely and effectively ablated the targeted treatment volumes in all subjects, demonstrating its potential to serve as a non-invasive treatment modality for primary bone tumors.
- Imaging of the Canine Heart Using Non ECG-Gated and ECG-Gated 64 Multidetector Computed TomographySaulnier, Diane Christine (Virginia Tech, 2012-07-11)ECG-gated multidetector computed tomography (MDCT) is an imaging modality widely utilized for the evaluation of cardiac pathology by physicians. However, there has been little research of cardiac MDCT imaging in veterinary patients. Presently, ECG-gating is an upgrade for MDCT, which few veterinary institutions currently possess. The purpose of this study was to compare image quality between a 16 non ECG-gated and 64 ECG-gated MDCT for clinically important cardiac anatomy in dogs. In a crossover trial, six dogs were scanned using 16 non ECG-gated and 64 ECG-gated MDCT. A standardized anesthetic protocol, designed to induce bradycardia (mean HR 45 bpm ± 12.6) was used. Five post-contrast sequential scans through the heart were performed for each patient when utilizing the 16 non ECG-gated MDCT, in attempt to obtain a motion free series of images of the heart. For each scan, assessment of cardiac morphology was performed by evaluating a group of 21 cardiac structures, using a 3-point scale. Each of the images were scored as 0 (motion present, scan non-diagnostic), 1 (motion present, scan diagnostic), and 2 (no motion, therefore diagnostic scan of high quality). Quality scores (QS) from all scans within a dog (30 scans total) were assigned for each cardiac structure. QS from the six ECG-gated MDCT scans were of high diagnostic quality, generating diagnostic images for all of the 21 cardiac structures evaluated for each of the 6 scans. Individual non ECG-gated scans were of variable quality, primarily generating QS of 1 or 2. A complete set of diagnostic images for all 21 structures was not achieved from an individual scan. Minimum number of non ECG-gated scans to identify a single structure was calculated, and ranged from 1-2 scans for all structures. Cumulative number of sequential non ECG-gated scans needed to achieve images of all cardiac structures was calculated and determined to be 5. A 16 non ECG-gated MDCT scanner can produce cardiac images that are similar in quality, to those of 64 ECG-gated MDCT. Cardiac motion negatively impacts image quality in studies acquired without ECG-gating. However, this can be overcome by performing multiple sequential scans through the heart.
- Investigation of a novel modified fixed dose determination protocol for radioiodine treatment of feline hyperthyroidismWentworth-Morre, Wendy Ann (Virginia Tech, 2017-05-24)Background: Radioiodine is the treatment of choice for feline hyperthyroidism. The ideal method of dose determination of 131I remains controversial. Objective: To compare a method of radioiodine dose determination that utilized thyroid scintigraphy with a standard fixed dose for treatment of feline hyperthyroidism. Methods: Fifty-seven and 23 cats were in the novel and fixed dose groups, respectively. Cats with a percent dose uptake as determined using 99mTcO4- uptake on thyroid scintigraphy <5%, 5-10%, and >10% were designated to receive 3 mCi, 3.5 mCi, or 4.5 mCi of 131I, respectively, administered subcutaneously. Radioiodine dose was adjusted by thyroid size, determined by evaluating the thyroid:salivary size ratio (T:S) and categorized as <5, 5-10, and >10. If the thyroid size fell into a higher dosing category than percent uptake, the dose was increased accordingly. Cats in the fixed dose group received 4.5 mCi of 131I. Six months after treatment, cats were determined to be euthyroid, hypothyroid, or hyperthyroid based on serum T4 concentrations relative to an established reference interval. Univariate analysis using Chi-square was used to determine associations between treatment and outcome. Results: There was no difference in outcome between the novel and fixed dose treatments. Euthyroidism, hypothyroidism, and hyperthyroidism developed in 61, 30, and 9% of cats in the fixed dose group, respectively compared to 58, 26, and 16% in the novel dose group. Conclusions: A modified fixed dose method of radioiodine based upon thyroid size and percent dose uptake was ineffective in improving outcomes over a standard fixed dose method.
- Investigation of a novel variable dosing protocol for radioiodine treatment of feline hyperthyroidismMorre, Wendy A.; Panciera, David L.; Daniel, Gregory B.; Monroe, William E.; Werre, Stephen R. (Wiley, 2018-11-01)Background: Radioiodine is the treatment of choice for hyperthyroidism in cats. The ideal method of dose determination of radioiodine remains controversial. Objective: To compare a method of radioiodine dose determination that utilized thyroid scintigraphy with a standard fixed dose for treatment of hyperthyroidism. Animals: Fifty-seven and 23 client-owned hyperthyroid cats in the variable and fixed dose groups, respectively. Methods: Cats with a percent dose uptake using 99mTc-pertechnetate uptake on thyroid scintigraphy <5%, 5%-10%, and >10% were to receive 3, 3.5, or 4.5 millicuries (mCi) of radioiodine, respectively, administered SC. Radioiodine dose was adjusted according to thyroid gland size as determined by the thyroid:salivary size ratio and categorized as <5:1, 5-10:1, and >10:1. If the thyroid size fell into a higher dosing category than the percent dose uptake, the dose was increased accordingly. Cats in the fixed dose group received 4.5 mCi. Six months after treatment, cats were determined to be euthyroid, hypothyroid, or hyperthyroid based on serum thyroxine and thyroid stimulating hormone concentrations. Results: No difference in outcome was found between the variable and fixed dose treatment groups. Euthyroidism, hypothyroidism, and persistent hyperthyroidism developed in 61, 30, and 9% of cats in the fixed dose group compared to 58, 26, and 16%, respectively, in the variable dose group. Conclusions: A variable dosing method of radioiodine based on percent dose uptake primarily and thyroid gland size secondarily did not improve outcome compared to a standard fixed dose method.
- Invited Review-Neuroimaging Response Assessment Criteria for Brain Tumors in Veterinary PatientsRossmeisl, John H. Jr.; Garcia, Paulo A.; Daniel, Gregory B.; Bourland, John Daniel; Debinski, Waldemar; Dervisis, Nikolaos G.; Klahn, Shawna L. (Wiley-Blackwell, 2014-03-01)
- Mechanical High-Intensity Focused Ultrasound (Histotripsy) in Dogs with Spontaneously Occurring Soft Tissue SarcomasRuger, Lauren N.; Yang, Ester; Gannon, Jessica; Sheppard, Hannah; Coutermarsh-Ott, Sheryl; Ziemlewicz, Timothy J.; Dervisis, Nikolaos G.; Allen, Irving C.; Daniel, Gregory B.; Tuohy, Joanne L.; Vlaisavljevich, Eli; Klahn, Shawna L. (IEEE, 2023-03)Introduction: Histotripsy is a non-invasive focused ultrasound therapy that uses controlled acoustic cavitation to mechanically disintegrate tissue. To date, there are no reports investigating histotripsy for the treatment of soft tissue sarcoma (STS). Objective: This study aimed to investigate the in vivo feasibility of ablating STS with histotripsy and to characterize the impact of partial histotripsy ablation on the acute immunologic response in canine patients with spontaneous STS. Methods: A custom 500 kHz histotripsy system was used to treat ten dogs with naturally occurring STS. Four to six days after histotripsy, tumors were surgically resected. Safety was determined by monitoring vital signs during treatment and post-treatment physical examinations, routine lab work, and owners’ reports. Ablation was characterized using radiologic and histopathologic analyses. Systemic immunological impact was evaluated by measuring changes in cytokine concentrations, and tumor microenvironment changes were evaluated by characterizing changes in infiltration with tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) using multiplex immunohistochemistry and differential gene expression. Results: Results showed histotripsy ablation was achievable and well-tolerated in all ten dogs. Immunological results showed histotripsy induced pro-inflammatory changes in the tumor microenvironment. Conclusion & Significance: Overall, this study demonstrates histotripsy's potential as a precise, non-invasive treatment for STS.
- Non-coagulopathic hemothorax in a dog: A case reportLaVine, Danielle; Conner, Bobbi; Daniel, Gregory B.; Freeman, Mark D. (Wiley, 2022-09)An 8-year-old, female-spayed, Blue Heeler presented with suspected non-coagulopathic spontaneous, hemothorax with neoplasia as the most likely differential as coagulation parameters were normal and no obvious history of trauma was reported. Computed tomography scan was crucial for diagnosis of a traumatic partial vascular avulsion injury that was successfully managed supportively.
- Non-Thermal Irreversible Electroporation (N-TIRE) and Adjuvant Fractionated Radiotherapeutic Multimodal Therapy for Intracranial Malignant Glioma in a Canine PatientGarcia, Paulo A.; Pancotto, Theresa E.; Rossmeisl, John H. Jr.; Henao-Guerrero, Natalia; Gustafson, N. R.; Daniel, Gregory B.; Robertson, John L.; Ellis, Thomas L.; Davalos, Rafael V. (Adenine Press, 2011-02-01)Non-thermal irreversible electroporation (N-TIRE) has shown promise as an ablative therapy for a variety of soft-tissue neoplasms. Here we describe the therapeutic planning aspects and first clinical application of N-TIRE for the treatment of an inoperable, spontaneous malignant intracranial glioma in a canine patient. The N-TIRE ablation was performed safely, effectively reduced the tumor volume and associated intracranial hypertension, and provided sufficient improvement in neurological function of the patient to safely undergo adjunctive fractionated radiotherapy (RT) according to current standards of care. Complete remission was achieved based on serial magnetic resonance imaging examinations of the brain, although progressive radiation encephalopathy resulted in the death of the dog 149 days after N-TIRE therapy. The length of survival of this patient was comparable to dogs with intracranial tumors treated via standard excisional surgery and adjunctive fractionated external beam RT. Our results illustrate the potential benefits of N-TIRE for in vivo ablation of undesirable brain tissue, especially when traditional methods of cytoreductive surgery are not possible or ideal, and highlight the potential radiosensitizing effects of N-TIRE on the brain.
- Quantitative Pertechnetate Thyroid Scintigraphy and the Ultrasonographic Appearance of the Thyroid Gland in Clinically Normal HorsesDavies, Sarah Elizabeth (Virginia Tech, 2010-04-28)The purpose of this study was to report the scintigraphic and sonographic appearance of the thyroid gland in clinically normal horses so these modalities could be used to assess the thyroid gland in this species. Horses were divided into two age groups. Group A consisted of 8 horses between 3 and 10 years of age and Group B of 7 horses between 11 and 20 years of age. Total T4 concentrations were within the laboratory reference interval. Thyroid to salivary (T/S) ratio, percent dose uptake of pertechnetate and thyroid lobe volume were calculated. Echogenicity of thyroid lobes and presence of nodules were documented. The two groups were compared using appropriate parametric and nonparametic tests. Total T4 concentrations were significantly lower in the older group. Sixty minute mean ± standard deviation (SD) T/S ratios for older versus younger horses were 5.8 ± 3.0 and 5.3 ± 2.2, respectively. Sixty minute median and interquartile ranges for percent dose uptake of pertechnetate for older versus younger horses were 3.64% (1.5 to 3.98%) and 2.55% (2.33 to 2.90%), respectively. Mean ± SD thyroid lobe volumes for older versus younger horses were 18.93 ± 5.16 cm3 and 13.55 ± 3.56 cm3, respectively. Most thyroid lobes were hyper or isoechoic to the sternocephalicus muscle. Prevalence of thyroid nodules did not differ between groups. Older horses had trends for greater T/S ratios, percent dose uptakes and thyroid lobe volumes but had lower total T4 concentrations. Further studies using scintigraphy and ultrasound in horses with thyroid disease are planned.