Patrick R. Gavin

Physical Principles and Technical Considerations for Equine Computed Tomography and Magnetic Resonance Imaging

This article discusses how cross-sectional imaging methods such as computed tomography and magnetic resonance imaging can provide unique and diagnostically important information in situations where radiography or diagnostic ultrasound have been unrewarding.

A review: CNS effects and normal tissue tolerance in dogs.

Large animal studies have been utilized to definetolerance of normal brain to irradiation and verifytreatment planning programs with two recently installed epithermalneutron beams.The normal brain tolerance studies utilized two biologicalendpoints, magnetic resonance visible damage only and neurologicsigns progressing to death. The studies focused ondefining the proton RBE for the contaminant fastneutrons, and from nitrogen capture of thermal neutronsand boron capture reaction biologic effect. The protonRBE was approximately 3.0 to 6.7, depending onwhether a dose reduction factor for the lowgamma dose rate was employed.The microscopic distribution of the boron compounds, coupledwith the extremely short length of the fissionfragments from thermal neutron capture by 10B yieldsan observed biologic effect much less than wouldbe expected from such high LET irradiation. Thisobserved biologic effect, which is a product ofthe microdistribution of the boron atom and therelative biologic effect of the fission fragments hasbeen termed compound factor. The compound factor wasbased on the calculated physical dose from thefission fragment in blood based on measured blood10B concentration. The approximate compound factor for BSHwas studied at the two institutions and itranged from 0.27 to 0.55, depending on thesite and the endpoint chosen. The mean compoundfactor for BPA was only studied at onesite and was found to be 1.1 forboth endpoints. The increase in the compound factorfor BPA is in keeping with previous calculationsbased on the differences in compound distribution. Resultsof these studies has helped the initiation ofphase I and phase II clinical trials atBrookhaven National Laboratory and the planned European clinicaltrials at Petten, The Netherlands.

Practical small animal MRI.

Preface. 1. Physics. Section 1. Comparative Imaging ( Patrick R. Gavin ) Section 2. Basic Physics ( Patrick R. Gavin ). Section 3. Sequence Selection ( Patrick R. Gavin ). Section 4. Artifacts ( Patrick R. Gavin ). Section 5. Equipment Consideration and Selection ( Patrick R. Gavin ). 2. Veterinary Clinical Magnetic Resonance Imagin. Section 1. Diagnosis of Intracranial Disease ( Rodney S. Bagley, Patrick R. Gavin, and Shannon P. Holmes ). Section 2. Diagnosis of Spinal Disease ( Rodney S. Bagley, Patrick R. Gavin, and Shannon P. Holmes ). Section 3. Magnetic Resonance Imaging of Peripheral Nerve Disease ( Rodney S. Bagley, Patrick R. Gavin, and Shannon P. Holmes ). 3. Orthopedic ( Patrick R. Gavin and Shannon P. Holmes ). 4. Magnetic Resonance Imaging of Abdominal Disease ( Patrick R. Gavin and Shannon P. Holmes ). 5. Thorax ( Patrick R. Gavin and Shannon P. Holmes ). 6. Head-Non-CNS ( Patrick R. Gavin and Shannon P. Holmes ). 7. Cancer Imaging ( Susan L. Kraft ). Index.

P-glycoprotein contributes to the blood-brain, but not blood-cerebrospinal fluid, barrier in a spontaneous canine p-glycoprotein knockout model.

P-glycoprotein is considered to be a major factor impeding effective drug therapy for many diseases of the central nervous system (CNS). Thus, efforts are being made to gain a better understanding of P-glycoproteins role in drug distribution to brain parenchyma and cerebrospinal fluid (CSF). The goal of this study was to validate and introduce a novel P-glycoprotein–deficient (ABCB1-1Δ) canine model for studying P-glycoprotein–mediated effects of drug distribution to brain tissue and CSF. CSF concentrations of drug are often used to correlate efficacy of CNS drug therapy as a surrogate for determining drug concentration in brain tissue. A secondary goal of this study was to investigate the validity of using CSF concentrations of P-glycoprotein substrates to predict brain tissue concentrations. Loperamide, an opioid that is excluded from the brain by P-glycoprotein, was used to confirm a P-glycoprotein–null phenotype in the dog model. ABCB1-1Δ dogs experienced CNS depression following loperamide administration, whereas ABCB1 wild-type dogs experienced no CNS depression. In summary, we have validated a novel P-glycoprotein–deficient canine model and have used the model to investigate transport of the P-glycoprotein substrate 99mTc-sestamibi at the blood-brain barrier and blood-CSF barrier.

Seizures as a Complication of Brain Tumors in Dogs

Seizures are a common reflection of a variety of intracranial physiologic abnormalities in dogs. In dogs with brain tumors, seizures often provide the clinical clue to the existence of an underlying structural brain disease. The majority of brain tumors that result in seizures affect the supratentorial nervous system, especially the olfactory and frontal lobes. Diagnosis requires advanced imaging such as computed tomography (CT) or magnetic resonance imaging (MRI) to establish the presence of a structural abnormality. Therapy is directed both at tumor and seizure control to afford the best chance of successful management of dogs with brain tumors.

Large animal normal tissue tolerance with boron neutron capture

PURPOSE Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA2B12H11SH) in an epithermal neutron beam was studied. METHODS AND MATERIALS Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. RESULTS Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. CONCLUSION The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood.

Radiation response of the canine cardiovascular system

GAVIN, P. R., AND GILLETTE, E. L. Radiation Response of the Canine Cardiovascular System. Radiat. Res. 90, 489-500 (1982). The hearts of dogs were irradiated with 60Co 7 rays. The dose required to produce pericardial effusion in 50% of the dogs by 180 days (PED50/180) was 1220 rad. For cardiac tamponade, the CTDo0/180 was 1500 rad. Morphometric analyses of the hearts showed decreased capillary volume and increased fibrosis as radiation dose increased. The pericardial thickness increased with increased radiation dose. The slopes of the dose response for these parameters were similar as determined by linear regression of the parameter versus radiation dose.

Large Animal Model Studies of Normal Tissue Tolerance Using an Epithermal Neutron Beam and Borocaptate Sodium

Epithermal neutron beams are being developed for potential boron neutron capture therapy (BNCT) to allow treatment of deep seated tumors, like glioblastoma multiforme, through the intact skin. The neutron capture cross-sections for elements in normal tissue are several orders of magnitude lower than that for boron but due to the relatively high concentrations of hydrogen and nitrogen in normal tissue, their capture through the 1H(n,γ)2H and the 14N(n,p)14C reactions respectively contribute significantly to the total radiation absorbed dose. Additional sources which contribute to the absorbed radiation dose are incident gamma-radiation and fast neutrons, i.e. components in the epithermal neutron beam.

Surgical treatment of mineralized and nonmineralized supraspinatus tendinopathy in twenty-four dogs.

OBJECTIVE To report and compare the clinical diagnosis, surgical treatment, histopathologic changes, and outcomes of dogs with mineralized and nonmineralized supraspinatus tendinopathy (ST). STUDY DESIGN Case series. ANIMALS Dogs (n=24) with ST. METHODS Medical records (1995-2006) of dogs with ST that had surgical treatment were reviewed. Results of clinical examination, diagnostic imaging, surgery, histopathology of resected tendon tissue, and outcome were compared between dogs with mineralized and nonmineralized ST. RESULTS There were 15 dogs with mineralized ST and 9 with nonmineralized ST. Chronic, unilateral, intermittent or waxing-waning lameness, and pain elicited on palpation of the cranial aspect of the shoulder were the most consistent findings. On ultrasonographic or magnetic resonance imaging (MRI) of 35 shoulders, enlargement of the supraspinatus tendon (54%), increased fluid content (63%), and medial displacement of the biceps tendon (60%) were observed. Eleven of 12 dogs with bilateral abnormalities only had unilateral lameness. Surgery was performed in 30 shoulders. Resected tendon specimens had myxomatous degeneration and/or cartilaginous metaplasia in 11 of 13 dogs in the mineralized group and all 9 dogs in the nonmineralized group. Functional outcome after surgery was poor in 3 dogs and good-to-excellent in 16. CONCLUSIONS Mineralized and nonmineralized ST have many similarities. Although lameness is usually unilateral, the supraspinatus tendon may be affected bilaterally. CLINICAL RELEVANCE Ultrasonography and MRI are good imaging techniques for detection of ST especially the nonmineralized form. Surgical treatment results in good recovery of limb function. Nonmineralized ST is a recently described disorder in dogs and evaluation of more cases is necessary to determine outcome after surgical or medical treatment.

Linear-Accelerator-Based Modified Radiosurgical Treatment of Pituitary Tumors in Cats: 11 Cases (1997–2008)

OBJECTIVE Determine the efficacy and safety of a linear-accelerator-based single fraction radiosurgical approach to the treatment of pituitary tumors in cats. DESIGN Retrospective study. ANIMALS Eleven client-owned cats referred for treatment of pituitary tumors causing neurological signs, or poorly controlled diabetes mellitus (DM) secondary either to acromegaly or pituitary-dependent hyperadrenocortism. PROCEDURES Cats underwent magnetic resonance imaging (MRI) of the brain to manually plan radiation therapy. After MRI, modified radiosurgery was performed by delivering a single large dose (15 or 20 Gy) of radiation while arcing a linear-accelerator-generated radiation beam around the cats head with the pituitary mass at the center of the beam. Eight cats were treated once, 2 cats were treated twice, and 1 cat received 3 treatments. Treated cats were evaluated for improvement in endocrine function or resolution of neurological disease by review of medical records or contact with referring veterinarians and owners. RESULTS Improvement in clinical signs occurred in 7/11 (63.6%) of treated cats. Five of 9 cats with poorly regulated DM had improved insulin responses, and 2/2 cats with neurological signs had clinical improvement. There were no confirmed acute or late adverse radiation effects. The overall median survival was 25 months (range, 1-60), and 3 cats were still alive. CONCLUSIONS AND CLINICAL IMPORTANCE Single fraction modified radiosurgery is a safe and effective approach to the treatment of pituitary tumors in cats.