Morphometric study of the ventricular indexes in healthy ovine BRAIN using MRI.

BACKGROUND: Sheep (Ovis aries) have been largely used as animal models in a multitude of specialties in biomedical research. The similarity to human brain anatomy in terms of brain size, skull features, and gyrification index, gives to ovine as a large animal model a better translational value than small animal models in neuroscience. Despite this evidence and the availability of advanced imaging techniques, morphometric brain studies are lacking. We herein present the morphometric ovine brain indexes and anatomical measures developed by two observers in a double-blinded study and validated via an intra- and inter-observer analysis. RESULTS: For this retrospective study, T1-weighted Magnetic Resonance Imaging (MRI) scans were performed at 1.5 T on 15 sheep, under general anaesthesia. The animals were female Ovis aries, in the age of 18-24 months. Two observers assessed the scans, twice time each. The statistical analysis of intra-observer and inter-observer agreement was obtained via the Bland-Altman plot and Spearman rank correlation test. The results are as follows (mean ± Standard deviation): Indexes: Bifrontal 0,338 ± 0,032 cm; Bicaudate 0,080 ± 0,012 cm; Evans' 0,218 ± 0,035 cm; Ventricular 0,241 ± 0,039 cm; Huckman 1693 ± 0,174 cm; Cella Media 0,096 ± 0,037 cm; Third ventricle ratio 0,040 ± 0,007 cm. Anatomical measures: Fourth ventricle length 0,295 ± 0,073 cm; Fourth ventricle width 0,344 ± 0,074 cm; Left lateral ventricle 4175 ± 0,275 cm; Right lateral ventricle 4182 ± 0,269 cm; Frontal horn length 1795 ± 0,303 cm; Interventricular foramen left 1794 ± 0,301 cm; Interventricular foramen right 1,78 ± 0,317 cm. CONCLUSIONS: The present study provides baseline values of linear indexes of the ventricles in the ovine models. The acquisition of these data contributes to filling the knowledge void on important anatomical and morphological features of the sheep brain.

High dose hypofractionated frameless volumetric modulated arc radiotherapy is a feasible method for treating canine trigeminal nerve sheath tumors.

The aim of this prospective pilot study was to evaluate the feasibility and effectiveness of curative intent high dose hypofractionated frameless volumetric modulated arc radiotherapy for treatment of canine trigeminal peripheral nerve sheath tumors. Client-owned dogs with a presumptive imaging-based diagnosis of trigeminal peripheral nerve sheath tumor were recruited for the study during the period of February 2010 to December 2013. Seven dogs were enrolled and treated with high dose hypofractionated volumetric modulated arc radiotherapy delivered by a 6 MV linear accelerator equipped with a micro-multileaf beam collimator. The plans were computed using a Monte Carlo algorithm with a prescription dose of 37 Gy delivered in five fractions on alternate days. Overall survival was estimated using a Kaplan-Meier curve analysis. Magnetic resonance imaging (MRI) follow-up examinations revealed complete response in one dog, partial response in four dogs, and stable disease in two dogs. Median overall survival was 952 days with a 95% confidence interval of 543-1361 days. Volumetric modulated arc radiotherapy was demonstrated to be feasible and effective for trigeminal peripheral nerve sheath tumor treatment in this sample of dogs. The technique required few sedations and spared organs at risk. Even though larger studies are required, these preliminary results supported the use of high dose hypofractionated volumetric modulated arc radiotherapy as an alternative to other treatment modalities.

FEASIBILITY FOR USING HYPOFRACTIONATED STEREOTACTIC VOLUMETRIC MODULATED ARC RADIOTHERAPY (VMAT) WITH ADAPTIVE PLANNING FOR TREATMENT OF THYMOMA IN RABBITS: 15 CASES.

Thymoma is a relatively common tumor in rabbits. Treatment with surgery, radiation therapy, and chemotherapy alone or in combination has been reported with varying outcomes. Stereotactic volumetric modulated arc radiotherapy delivered in a hypofractionated manner allows high doses of radiation to be delivered to the target volume while allowing sparing of adjacent critical structures. This therapy is ideally suited for thymomas in rabbits given their size, the difficulty of multiple anesthesia episodes and the complexity of the radiotherapy plans required due to the tumor's proximity to the heart, lungs, and mediastinal structures. Fifteen rabbits with thymoma were prospectively recruited for this observational, single institution, single arm clinical study. All rabbits were imaged with both computed tomography (CT) and magnetic resonance imaging (MRI). A total dose of 40 Gy in six fractions was delivered using a single arc over an 11-day period with repeat CT simulation done every other fraction for adaptive planning. Follow-up evaluation was done through repeat CT and MRI imaging and revealed complete responses using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Two rabbits had died at 618 and 718 days, 10 were alive and three were lost to follow-up. Observed acute and late effects were graded according to the Veterinary Radiation Therapy Oncology Group (VRTOG) criteria and were found to be minimal.

A Combined Hypofractionated Volumetric Modulated Arc Radiotherapy, Radio-Sensitising and Adjuvant Metronomic Chemotherapy Treatment for Canine Stage IV Nasal Tumours With Intracranial Extension.

Radiation therapy has become the standard of care in the treatment of canine intranasal neoplasia, but because of the poor prognosis associated with stage IV nasal tumours and the proximity of the brain to the irradiation target, few data regarding the treatment of very advanced neoplasms are available. The aim of this pilot study was to evaluate the feasibility, safety and effectiveness of a combined treatment composed of definitive high-dose hypofractionated volumetric modulated arc radiotherapy on tumours with concurrent treatment of regional lymph nodes if positive or as prophylaxis, carboplatin radio-sensitising, and adjuvant metronomic chemotherapy for stage IV canine nasal tumours with intracranial extension. A pilot observational study was conducted in 7 dogs. Magnetic resonance imaging follow-up examinations revealed complete responses in 5 dogs and partial responses in 2. The median overall survival time, evaluated via Kaplan-Meier survival analysis, was 310 days with a 95% confidence interval of 210-400 days, whereas the median progression-free survival was 240 days with a 95% confidence interval of 190-290 days. Despite the proximity of highly sensitive organs at risk, no grade III or IV toxicities were observed, and volumetric modulated arc radiotherapy seemed to be a feasible treatment option for stage IV canine nasal tumours where conformal 3D radiotherapy has proven to give higher doses with severe damage to the surrounding unaffected tissues. Further studies are needed on the role of the sphenoid bone microscopic infiltration and regional lymph node involvement. The absence of severe toxicity could also lead to a dose escalation study and chemotherapy scheme.

Cranial Spinal Spreading of Canine Brain Gliomas after Hypofractionated Volumetric-Modulated Arc Radiotherapy and Concomitant Temozolomide Chemotherapy: A Four-Case Report.

Gliomas are the second-most-common primary brain tumors in dogs. Surgery and radiotherapy are established treatment approaches with similar median survival time, whereas conventional chemotherapy is burdened by severe adverse effects. Spinal and leptomeningeal spread of gliomas have been described following radiotherapy treatment alone. The purpose of this study was to evaluate the outcome for four dogs with primary high-grade gliomas in the forebrain without evidence, at diagnosis, of neoplastic invasion along the spinal cord, that were treated with concomitant chemotherapy (temozolomide) and hypofractionated volumetric-modulated arc radiotherapy (VMAT-RT). Temozolomide was selected for its radiosensitive properties, and radiotherapy dose protocols of 37 Gy in 7 fractions or 42 Gy in 10 fractions were used. After an initial complete or partial response, tumors recurred across the cranial-spinal pathway. Post-mortem macroscopic examinations confirmed swollen spinal cord and hyperemic meningeal sleeve, with nodular lesions on the meningeal surface. Microscopically, infiltration of the spinal cord and meninges by neoplastic cells (with features of oligodendrogliomas) were observed. This work seems to suggest that the entire central nervous system should be investigated in diagnostic examinations of canine gliomas. Dose-escalation trials and/or spinal cord prophylaxis treatment could also be evaluated to prevent tumor progression.

A combined protocol with piroxicam, chemotherapy, and whole pelvic irradiation with simultaneous boost volumetric modulated arc radiotherapy for muscle-invasive canine urinary transitional cell carcinoma: First clinical experience.

The aims of this pilot study were to evaluate the feasibility and efficacy of high-dose hypofractionated volumetric modulated arc radiotherapy (VMAT) applied to whole pelvic region radiotherapy (WPRT) with multilevel simultaneous integrated boost (MLSIB) combined with piroxicam and chemotherapy for the treatment of canine transitional cell carcinoma (TCC) of the lower urinary tract with muscle invasion TCC. Twelve dogs were enrolled, according to stage, in two groups: group 1, TCC confined to the urinary tract; group 2, TCC with metastasis. The planning target volume dose was tailored from 36 to 42 Gy in 6 fractions. All dogs were prescribed piroxicam and radiosensitizing carboplatin, and six received chemotherapy after radiotherapy. Serial follow-ups with computed tomography and magnetic resonance imaging were performed. Disease control and toxicity effects were evaluated according to the Response Evaluation Criteria in Solid Tumors and Veterinary Radiation Therapy Oncology Group criteria. The treatment was well tolerated, and no high-grade side effects were reported. The median overall survival times for groups 1 and 2 were 1,230 and 150 days, respectively. A considerable percentage of patients in group1 (50%) were still alive at the time of writing this paper, and a longer follow-up could enable a more accurate survival analysis. This preliminary analysis shows that VMAT applied to the WPRT with MLSIB is an effective and safe option for dogs with lower urinary TCC, although the presence of metastases worsens the prognosis.

In vivo Diffusion Tensor Magnetic Resonance Tractography of the Sheep Brain: An Atlas of the Ovine White Matter Fiber Bundles.

Diffusion Tensor Magnetic Resonance Imaging (DTI) allows to decode the mobility of water molecules in cerebral tissue, which is highly directional along myelinated fibers. By integrating the direction of highest water diffusion through the tissue, DTI Tractography enables a non-invasive dissection of brain fiber bundles. As such, this technique is a unique probe for in vivo characterization of white matter architecture. Unraveling the principal brain texture features of preclinical models that are advantageously exploited in experimental neuroscience is crucial to correctly evaluate investigational findings and to correlate them with real clinical scenarios. Although structurally similar to the human brain, the gyrencephalic ovine model has not yet been characterized by a systematic DTI study. Here we present the first in vivo sheep (ovis aries) tractography atlas, where the course of the main white matter fiber bundles of the ovine brain has been reconstructed. In the context of the EU's Horizon EDEN2020 project, in vivo brain MRI protocol for ovine animal models was optimized on a 1.5T scanner. High resolution conventional MRI scans and DTI sequences (b-value = 1,000 s/mm2, 15 directions) were acquired on ten anesthetized sheep o. aries, in order to define the diffusion features of normal adult ovine brain tissue. Topography of the ovine cortex was studied and DTI maps were derived, to perform DTI tractography reconstruction of the corticospinal tract, corpus callosum, fornix, visual pathway, and occipitofrontal fascicle, bilaterally for all the animals. Binary masks of the tracts were then coregistered and reported in the space of a standard stereotaxic ovine reference system, to demonstrate the consistency of the fiber bundles and the minimal inter-subject variability in a unique tractography atlas. Our results determine the feasibility of a protocol to perform in vivo DTI tractography of the sheep, providing a reliable reconstruction and 3D rendering of major ovine fiber tracts underlying different neurological functions. Estimation of fiber directions and interactions would lead to a more comprehensive understanding of the sheep's brain anatomy, potentially exploitable in preclinical experiments, thus representing a precious tool for veterinaries and researchers.

VMAT Stereotactic Body Radiation Therapy in a Multimodal Approach to a Carotid Paraganglioma in a Dog.

A 7 yr old female pit bull terrier was presented for a cervical soft tissue swelling located in the left jugular region. No abnormalities were present at physical examination or in the laboratory workup. Computed tomography and MRI scans showed a well-defined, ovoid, single mass in the left dorsal cervical region connected to the common carotid artery, histologically consistent with carotid body paraganglioma. The mass was surgically resected. Frameless stereotactic body radiation therapy with volumetric modulated arc therapy was set up as adjuvant treatment. After radiation therapy, systemic chemotherapy with carboplatin was started. During the first yr of follow-up, acute grade I dermatitis and grade I left-side laryngeal mucositis were recognized. One yr after radiation therapy, no signs of late radiotoxicity or tumor recurrence were observed. Grade I thrombocytopenia concurrent with chemotherapy was observed. This is the first reported case of a carotid body paraganglioma treated by multimodal therapy, with surgical resection and adjuvant radiotherapy and chemotherapy. Stereotactic body radiation therapy with volumetric modulated arc therapy treatment after surgery provided excellent disease control and was well tolerated with slight side effects.

Stereotactic Volume Modulated Arc Radiotherapy in Canine Meningiomas: Imaging-Based and Clinical Neurological Posttreatment Evaluation.

A prospective study to assess high-dose hypofractionated volume modulated arc radiotherapy feasibility and efficacy in canine meningiomas was conducted. Thirty-nine patients with encephalic and spinal meningiomas assumed from MRI findings were recruited and received high-dose hypofractionated volumetric modulated arc radiotherapy by a linear accelerator equipped with an external beam modulator micro-multileaf collimator and an XVI cone beam computed tomography system. The prescribed mean dose was 33 Gy in five fractions. The treatment feasibility was tested through planned and delivered dose agreement checks. Regular clinical examinations were performed during and after irradiation time, with regard to mentation, deambulation, cranial nerve dysfunction, and seizures. Serial MRI exams were done 60 days after irradiation and after 4, 6, 12, 18, and 24 mo. Volumetric disease reduction criteria implemented with clinical neurological systematic evaluation were adopted to assess the course and to categorize patients' responses. Complete and partial responses were observed on the whole in 65.5% of alive patients 24 mo after irradiation. Two-yr overall and disease-specific survival rates were 74.3% and 97.4%, respectively, and the putative radiotoxic effects were found to be few and slight.

Volumetric Modulated Arc (Radio) Therapy in Pets Treatment: The "La Cittadina Fondazione" Experience.

Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in human radiotherapy, which allows a high dose to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinics takes advantage of this feature due to the small target volumes and distances between the target and the OAR. Sparing the OAR permits dose escalation, and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding missing the target. Additionally, the elaborate treatment plan must pursue hard constraints and objectives, and its feasibility must be evaluated with a per patient quality control. The aim of this work is to report results with regard to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal tumors with vascular invasion and rabbit thymomas, in comparison with literature to determine if VMAT is a safe and viable alternative to surgery or chemotherapy alone, or as an adjuvant therapy in pets.

Computed tomography, magnetic resonance imaging and a novel surgical approach of atlanto-axial instability with incongruence in dogs.

Atlanto-axial (AA) instability due to ligament insufficiency is a common cause of cervical spinal cord compression in toy breeds. However, in some dogs a difference in size between the atlas and the axis leads to joint incongruence that exacerbates AA subluxation and makes surgical treatment challenging. Twelve dogs with AA instability with incongruence were enrolled in a single institution prospective observational study. Computed tomography (CT) and magnetic resonance imaging (MRI) of the AA joint were compared to a retrospectively reviewed control group. A novel surgical approach consisting of a dorsal internal fixation technique was performed in six dogs. For affected dogs, the mean normalised difference between the dorso-ventral atlas canal and the dorso-ventral axis canal was 29.67% (median of 35.07%, standard deviation 25.64%), while in normal dogs a mean difference of 4.67% (median of 3.95%, standard deviation 5.21%) was observed. On MRI, 12/12 affected dogs had spinal cord compression, which was classified as reducible (3/12), partially reducible (6/12) and non-reducible (3/12). In surgically operated dogs, follow-up CT showed a partial or complete reduction of the previous spinal cord compression with a consistent amelioration or resolution of the presenting complaints. The proposed surgical technique was safe and effective in dogs with partially or completely reducible spinal cord compression.

Frameless stereotactic volumetric modulated arc radiotherapy of brachial plexus tumours in dogs: 10 cases.

OBJECTIVE: Treatment of canine peripheral nerve sheath tumours (PNSTs) is challenging and prognosis after surgical resection is considered poor. The aim of this study was to evaluate the feasibility and effectiveness of stereotactic radiotherapy (RT) of these tumours. METHODS: 10 dogs with clinical symptoms and MRI findings consistent with PNSTs of the brachial plexus, branches and nerve roots were treated with linear accelerator-based volumetric-modulated arc radiotherapy (VMAT) with a dose of 35 Gy/5 fractions. Clinical and MRI follow-up examinations were planned and radiotoxicity and survival times were investigated. RESULTS: Tumours involved the plexus and proximal nerves in three dogs, the plexus, proximal nerves and nerve roots in five dogs and the nerve roots and proximal nerves in two dogs. Partial response and partial or complete reductions of neurological deficits were observed in all the treated dogs. Local recurrence was observed in 9/10 of treated dogs. No symptom directly referable to radiotoxicity was observed. Mean overall survival of 371 ± 30 days [95% confidence interval (CI) of (315-427)] and mean progression-free survival of 240 ± 30 days (95% CI of 188-291) from this work are comparable with surgical literature data regarding the plexus and proximal nerve localization, but are superior in comparison with nerve root localization. CONCLUSION: VMAT can be a safe and viable alternative to surgery in cases of canine brachial plexus PNSTs involving the proximal nerves and nerve roots. Advances in knowledge: To our knowledge, this is the first prospective observational clinical study regarding VMAT stereotactic RT treatment for canine brachial plexus PNSTs and suggests that VMAT may achieve at least similar clinical outcome than surgery in a safer way.

Zygomatic arch-atlas wing stabilization in 5 dogs with atlanto-occipital dislocation.

The aim of this work was to present a novel minimally invasive surgical stabilization technique for canine atlanto-occipital dislocation and to report the associated magnetic resonance imaging (MRI) findings. All 5 dogs in this case series underwent 1.5 T MRI of the head and neck and 3 underwent both MRI and computed tomography (CT). Atlanto-occipital dislocations were diagnosed based on the increased joint space between the occipital condyles and the atlas on MRI. Surgery was performed immediately with a never previously described fixation technique based on an external ligature. The stabilization was performed via 4 holes drilled in the zygomatic processes and in the atlas wings on each side. A nylon monofilament of 1 mm diameter was inserted in the 4 holes, and an O-shaped ligature was carried out externally to the skin through the ipsilateral zygomatic arch. Ligatures were removed within 2 months. At the postsurgical follow-up examination, 14 days after surgery, all dogs were found to be ambulatory. Atlanto-occipital stability was assessed by clinical examination with an average of 24 months of follow-up. The positive outcomes in this case series suggest that atlanto-occipital dislocation may be surgically treated with this novel technique, irrespective of the severity of the clinical presentation and associated lesions observed on MRI.

Hydrated nucleus pulposus extrusion in dogs: correlation of magnetic resonance imaging and microsurgical findings.

BACKGROUND: Magnetic resonance imaging (MRI) patterns of canine cervical hydrated nucleus pulposus extrusion (HNPE) have been described by a few reports, but the correlation between microsurgical and MRI features has never been investigated. The aim of this study was to compare the MRI features of HNPE with microsurgical findings and cytological outcomes and also to investigate the anatomical and pathophysiological aspects of the disease. METHODS: A prospective clinical study was conducted in 36 dogs suffering from HNPE. The diagnosis was based on high-field MRI findings of ventral extradural lesions, adjacent to the dorsal aspect of intervertebral discs, characterised by high signal intensity in T2-weighted sequences and hypointensity in T1-weighted sequences. MRI images were analysed with regard to the intervertebral space involved, the grading of spinal cord compression, the signal intensity and distribution of the material, and the thickness and signal intensity of the involved discs. All patients underwent microsurgical decompression and direct observations were recorded and films of the surgical procedure analysed. RESULTS: The majority of patients had acute onset of clinical signs (78 %), the patient did not exhibit signs of pain in 75 % of dogs and neurological deficits varied from slight tetraparesis (33 %) to tetraplegia (28 %). The localization of the extruded disc material was ventral relative to the dorsal longitudinal ligament that was lifted dorsally and appeared intact at the site of compression. Direct microsurgical observations of the HNPE sites showed that extruded disc material was collected within the fibres of the dorsal longitudinal ligament. The consistency was gelatinous in 42 %, water-like in 33 %, and lumpy liquid in 25 % of cases. Cytological samples did not detect the presence of inflammation, bacteria, fungi, neoplastic cells or foreign material. CONCLUSIONS: Microsurgical features of HNPE suggest that the extruded disc is collected within the fibres of the dorsal longitudinal ligament and this may explain the typical MRI appearance of this disease. Further pathophysiological studies are needed to investigate why the cervical nucleus pulposus extrusion appears to occur without obvious trauma.