Safety and interim survival data after intracranial administration of M032, a genetically engineered oncolytic HSV-1 expressing IL-12, in pet dogs with sporadic gliomas.

OBJECTIVE: The diagnosis of glioma remains disheartening in the clinical realm. While a multitude of studies and trials have shown promise, improvements in overall survival have been disappointing. Modeling these tumors in the laboratory setting has become increasingly challenging, given their complex in situ behavior and interactions for therapeutic evasion. Dogs, particularly brachycephalic breeds, are known to spontaneously develop gliomas that resemble human gliomas both clinically and pathophysiologically, making canines with sporadic tumors promising candidates for study. Typically, survival among these dogs is approximately 2 months with palliation alone. METHODS: The authors have completed the first stage of a unique phase I dose-escalating canine clinical trial in which the safety and tolerability of M032, a nonneurovirulent oncolytic herpes simplex virus-1 vector genetically engineered to express interleukin-12, are being studied in pet dogs with gliomas undergoing maximum safe tumor resection and inoculation of the cavity with the viral infusate. RESULTS: Twenty-five canine patients were enrolled between January 2018 and August 2020. One patient was electively withdrawn from the trial by its owner, and 3 did not receive the virus. For the 21 dogs that remained, 13 had high-grade gliomas, 5 had low-grade gliomas, and 3 were undetermined. According to histopathological analysis, 62% of the tumors were oligodendrogliomas. At the time of this report, the median overall survival from the date of treatment was 151 days (± 78 days). No significant adverse events attributable to M032 or dose-limiting toxicities have been observed to date. CONCLUSIONS: In this largest study of oncolytic viral therapy for canine brain tumors to date, treatment with M032 did not cause harm and the combination of surgery and oncolytic viral therapy may have contributed to prolonged survival in pet dogs with spontaneous gliomas. Forthcoming in-depth radiographic, immunohistochemical, and genetic analyses will afford a more advanced understanding of how this treatment impacts these tumors and the immune system. Our goal is to utilize these findings bitranslationally to inform human studies and refine therapies that will improve outcomes in both humans and pet dogs with gliomas.

Piezoresistor-Embedded Multifunctional Magnetic Microactuators for Implantable Self-Clearing Catheter.

Indwelling catheters are used widely in medicine to treat various chronic medical conditions. However, chronic implantation of catheters often leads to a premature failure due to biofilm accumulation. Previously we reported on the development of a self-clearing catheter by integrating polymer-based microscale magnetic actuators. The microactuator provides an active anti-biofouling mechanism to disrupt and remove adsorbed biofilm on demand using an externally applied stimulus. During an in vivo evaluation of self-clearing catheter, we realized that it is important to periodically monitor the performance of implanted microactuators. Here we integrate gold-based piezoresistive strain-gauge on our magnetic microactuators to directly monitor the device deflection with good sensitivity (0.035%/Deg) and linear range (±30°). With the integrated strain-gauge, we demonstrate the multi-functional capabilities of our magnetic microactuators that enable device alignment, flow-rate measurement, and obstruction detection and removal towards the development of chronically implantable self-clearing smart catheter.

Remission after complete excision of an intramedullary hemangioma with an identifiable tumor plane in a dog.

OBJECTIVE: To describe the use of an identifiable tumor plane (ITP) during myelotomy to excise an intramedullary hemangioma in a dog and report the outcome. STUDY DESIGN: Case report. ANIMALS: One 5.5-year-old 42.9-kg spayed female Leonberger dog. METHODS: Clinical signs included progressive proprioceptive deficits of both pelvic limbs. Magnetic resonance imaging was consistent with a dorsal intramedullary mass at L3-L4. A laminectomy of the third and fourth lumbar vertebrae provided access for dorsal myelotomy. A clear surgical ITP was identified between the intramedullary mass and the spinal cord facilitating complete surgical resection. RESULTS: Histopathological examination was consistent with a hemangioma. Postoperative MRI was consistent with complete excision of the mass. No evidence of recurrence was found by MRI at 3 months and at 22 months after surgery. Mild proprioceptive deficits persisted in the right pelvic limb. CONCLUSION: A clear ITP was present, and gross-total resection (GTR) was achieved without significant morbidity. Persistent clinical remission resulted from surgery as the sole therapy. CLINICAL SIGNIFICANCE: For an intramedullary tumor, GTR is the absence of visible tumor on intraoperative inspection combined with the absence of intramedullary contrast enhancement on postoperative MRI. When an ITP is present, GTR and resultant long-term remission may be more likely.

Immunologic and gene expression profiles of spontaneous canine oligodendrogliomas.

Malignant glioma (MG), the most common primary brain tumor in adults, is extremely aggressive and uniformly fatal. Several treatment strategies have shown significant preclinical promise in murine models of glioma; however, none have produced meaningful clinical responses in human patients. We hypothesize that introduction of an additional preclinical animal model better approximating the complexity of human MG, particularly in interactions with host immune responses, will bridge the existing gap between these two stages of testing. Here, we characterize the immunologic landscape and gene expression profiles of spontaneous canine glioma and evaluate its potential for serving as such a translational model. RNA in situ hybridization, flowcytometry, and RNA sequencing were used to evaluate immune cell presence and gene expression in healthy and glioma-bearing canines. Similar to human MGs, canine gliomas demonstrated increased intratumoral immune cell infiltration (CD4+, CD8+ and CD4+Foxp3+ T cells). The peripheral blood of glioma-bearing dogs also contained a relatively greater proportion of CD4+Foxp3+ regulatory T cells and plasmacytoid dendritic cells. Tumors were strongly positive for PD-L1 expression and glioma-bearing animals also possessed a greater proportion of immune cells expressing the immune checkpoint receptors CTLA-4 and PD-1. Analysis of differentially expressed genes in our canine populations revealed several genetic changes paralleling those known to occur in human disease. Naturally occurring canine glioma has many characteristics closely resembling human disease, particularly with respect to genetic dysregulation and host immune responses to tumors, supporting its use as a translational model in the preclinical testing of prospective anti-glioma therapies proven successful in murine studies.

Anti-biofouling implantable catheter using thin-film magnetic microactuators.

Here we report on the development of polyimide-based flexible magnetic actuators for actively combating biofouling that occurs in many chronically implanted devices. The thin-film flexible devices are microfabricated and integrated into a single-pore silicone catheter to demonstrate a proof-of-concept for a self-clearing smart catheter. The static and dynamic mechanical responses of the thin-film magnetic microdevices were quantitatively measured and compared to theoretical values. The mechanical fatigue properties of these polyimide-based microdevices were also characterized up to 300 million cycles. Finally, the biofouling removal capabilities of magnetically powered microdevices were demonstrated using bovine serum albumin and bioconjugated microbeads. Our results indicate that these thin-film microdevices are capable of significantly reducing the amount of biofouling. At the same time, we demonstrated that these microdevices are mechanically robust enough to withstand a large number of actuation cycles during its chronic implantation.

IMAGING DIAGNOSIS -ANTEMORTEM DETECTION OF OLIGODENDROGLIOMA "CEREBROSPINAL FLUID DROP METASTASES" IN A DOG BY SERIAL MAGNETIC RESONANCE IMAGING.

An English Bulldog underwent radiation therapy of an intracranial, left lateral ventricle mass. Following resolution of the primary mass, an intraventricular fourth ventricle lesion developed. Subsequently, multiple lesions developed from the cervical central canal and leptomeninges. Serial magnetic resonance imaging documented the propagation of lesions along the cerebrospinal fluid (CSF) pathways, known as "CSF drop metastasis." Histopathology confirmed multifocal intraventricular and leptomeningeal oligodendroglioma. Oligodendroglioma should be included in the differential diagnosis for an intraventricular tumor exhibiting apparent CSF drop metastasis.

Radiographic indices for the diagnosis of atlantoaxial instability in toy breed dogs [corrected].

Toy breed dogs are overrepresented for atlantoaxial instability. Radiography is a standard diagnostic test, however published toy breed-specific radiographic measurements are lacking and diagnosis remains largely subjective. Aims of this retrospective, diagnostic accuracy study were to describe normal values and determine whether some quantitative radiographic criteria strongly support a diagnosis of atlantoaxial instability specific to toy breed dogs. Neutral lateral and ventrodorsal radiographs of 102 toy breed dogs (92 control, 10 affected) were reviewed. The median C1-C2 overlap (the distance of overlap between the C2 spinous process and the dorsal arch of C1) was +4.65 mm in control dogs and -5.00 mm in atlantoaxial instability cases. A C1-C2 overlap ≤ +1.55 mm was the most sensitive (100%) and specific (94.5%) radiographic measurement in the diagnosis of atlantoaxial instability. Three relative measurements were performed: the ventral atlantodental interval to dorsal atlantodental interval ratio, the dens/C2 ratio, and the C1-C2 angle. These three relative measurements had good specificity (94.5, 86.9, and 98.9%, respectively), lower sensitivity (80.0, 66.7, and 60.0%, respectively), and were not influenced by body weight (P > 0.05). Absolute measurements (including absolute dens length and atlantoaxial distance) were significantly correlated with body weight (P < 0.05) diminishing their utility in the diagnosis of atlantoaxial instability. Decreased C1-C2 overlap strongly supports atlantoaxial instability. The ventral atlantodental interval/dorsal atlantodental interval ratio, dens/C2 ratio, and C1-C2 angle may provide further support but may be normal in individual cases.

Safety and feasibility of stereotactic radiotherapy using computed portal radiography for canine intracranial tumors.

Stereotactic radiotherapy is a highly conformal treatment option for intracranial and extracranial malignancies. Stereotactic radiotherapy utilizes specialized equipment specifically designed to avoid normal tissue while delivering ablative treatments with submillimeter precision and accuracy. Linear accelerator based stereotactic radiotherapy incorporates on-board image guidance utilizing cone beam computed tomography (CT). Many institutions lack the ability to provide image guidance with cone beam CT but delivery of highly conformal treatments with submillimeter precision and accuracy is still feasible. The purpose of this retrospective, pilot study was to describe clinical outcomes for a group of dogs with neurological disease that were treated with an stereotactic radiotherapy technique utilizing intensity modulated radiation therapy, megavoltage computed portal radiography, a bite plate, thermoplastic mold, and mask based positioning system. Twelve dogs with neurological clinical signs were included. The diagnosis of intracranial tumor was made based on advanced imaging (12/12) and confirmed via histopathology (3/12). Twelve courses of stereotactic radiotherapy, utilizing three fractions of 8.0 Gy, were delivered on alternating days. Self-resolving neurological deterioration was observed in two patients during stereotactic radiotherapy. Neurological progression free interval and median survival time were 273 days (range: 16-692 days) and 361 days (range: 25-862 days). Stereotactic radiotherapy using computed portal radiography may be a safe treatment option for dogs with intracranial tumors.

SPINAL MAST CELL TUMORS IN DOGS: IMAGING FEATURES AND CLINICAL OUTCOME OF FOUR CASES.

Published information regarding canine vertebral column mast cell tumors (MCTs) is limited. The objectives of this study were to report clinical and advanced imaging findings for a group of dogs with confirmed spinal MCT. Inclusion criteria for this retrospective case series were dogs with spinal magnetic resonance imaging (MRI) or computed tomography (CT) scans and a histological diagnosis of spinal MCT. Clinical, imaging, treatment, and outcome data were recorded. Four dogs met inclusion criteria. One dog had primary spinal MCT and three dogs had metastatic spinal MCT. All four dogs presented for paraspinal hyperesthesia and subacute progressive or acute myelopathy. All CT and MRI lesions were extradural. Two cases exhibited distinct masses in the epidural space. In one case, an epidural tumor invaded from the paravertebral musculature. One case exhibited polyostotic lesions indistinguishable from multiple myeloma by MRI. One dog with a primary epidural low-grade MCT remains clinically normal 4 years postoperatively, following adjunctive lomustine. An epidural high-grade MCT, metastatic from a cutaneous tumor, recurred within 2 months of surgery despite adjunctive vinblastine. Two high-grade cases with concurrent visceral involvement were euthanized immediately after imaging. In dogs, MCT should be considered as a differential diagnosis for a progressive painful myelopathy and CT or MRI evidence of an extradural spinal lesion (epidural, paravertebral, or polyostotic). While more often associated with cutaneous or disseminated disease, MCT may also occur as a primary tumor of the epidural space in dogs.

A preliminary evaluation of the reliability of a modified functional scoring system for assessing neurologic function in ambulatory thoracolumbar myelopathy dogs.

BACKGROUND: The objective of this study was to develop and assess the reliability of a modified scoring system for evaluating the function of the two pelvic limbs separately, in ambulatory thoracolumbar myelopathy dogs. A previously established neurologic score scale for dogs with T3-L3 lesions was modified in order to provide a separate score for each pelvic limb. RESULTS: Seventeen ambulatory dogs with thoracolumbar myelopathies were evaluated. Using the new scale, two observers independently performed 22 observational gait analyses (OGAs) in ten dogs without videotape. Another 18 OGAs were performed in seven dogs by watching videotapes of them ambulating. There was poor agreement (concordance correlation coefficient, 0.87) between the two observers for all 40 OGAs. When stratified, the agreement was moderate (concordance correlation coefficient, 0.90) in the OGAs without videotaping and poor (concordance correlation coefficient, 0.80) for the OGAs based on videotapes. For the decision regarding which pelvic limb was more severely affected, a fair agreement (kappa value, 0.30) between the two observers was noted. Without videotape there was only slight agreement (kappa value, 0.05), but with videotape there was moderate agreement (kappa value, 0.56). CONCLUSIONS: The modified scoring system in this study provides moderate reliability in assessing the functional neurologic status of each pelvic limb, by OGA without videotape, in canine T3-L3 patients. Further development of this scoring system is required. However, imperfect agreement when visually quantifying neurological deficits is not unexpected.

MAGNETIC RESONANCE IMAGING FEATURES AND OUTCOME FOR SOLITARY CENTRAL NERVOUS SYSTEM COCCIDIOIDES GRANULOMAS IN 11 DOGS AND CATS.

Little published information is available to guide therapy for canine and feline patients with Coccidioides infections involving the central nervous system (CNS). The purpose of this cross-sectional retrospective study was to describe magnetic resonance imaging (MRI) features and outcome for a group of dogs and cats with solitary CNS Coccidiodes granulomas. Nine canine and two feline cases met inclusion criteria; four diagnosed and treated with surgery and fluconazole and seven diagnosed by serology or cytology and treated medically. Three cases had left Coccidioides endemic areas long before developing neurological disease. The MRI lesions shared many features with neoplastic masses. The extra-axial granulomas often had a lack of a distinct border between the mass and neural parenchyma. Four cases were extra-axial and seven were intra-axial, but distinguishing between extra-axial and intra-axial locations was sometimes challenging. The surgical cases had good outcomes and histology allowed definitive diagnosis. Medically managed patients also had generally good outcomes, with resolution of clinical signs in most cases. Findings indicated that distinction between neoplasia and focal Coccidioides granulomas based on MRI features is likely to be imprecise. Demonstration of the organism by cytology or histology is required for definitive diagnosis. The role of surgery for improving the outcome of brain or spinal coccidioidomycosis granulomas warrants further study.

Survival in dogs with meningoencephalomyelitis of unknown etiology with and without lesions detected by magnetic resonance imaging.

BACKGROUND: The prognosis of individual dogs with meningoencephalomyelitis of unknown etiology (MUE) remains difficult to predict. MUE cases with no lesions detected by magnetic resonance imaging (MRI) occur, but it is unknown whether this finding is associated with prognosis. HYPOTHESIS: MUE cases without detectable lesions on MRI have a better outcome than cases with detectable lesions. ANIMALS: Study included 73 client-owned dogs with MUE presenting to Purdue University Veterinary Hospital from 2010 to 2020. METHODS: Retrospective study. Dogs with a clinical diagnosis of MUE were identified by medical record search. MRI reports were reviewed for presence or absence of lesions consistent with MUE. Clinical findings at presentation, treatment, disease-specific survival, and outcomes including rates of remission and relapse were compared between cases with normal MRI or abnormal MRI. RESULTS: Overall, 54 dogs (74%) were classified as abnormal MRI, and 19 dogs (26%) were classified as normal MRI cases. Death caused by MUE occurred in 1/19 (5%) normal MRI dogs and 18/54 (33%) abnormal MRI dogs (P = .016). Median survival was >107 months in both groups, but survival was significantly longer in the normal MRI group (P = .019). On multivariate analysis, abnormal MRI was significantly related to death (hazard ratio, 7.71; 95% confidence interval 1.03-58.00, P = .0470), whereas significant relationships with death were not identified for either the use of secondary immunosuppressive medications or cerebrospinal fluid nucleated cell count. CONCLUSIONS: MUE dogs with no detectable lesions on MRI have reduced disease-related death compared with dogs with abnormal MRI. The presence or absence of MRI lesions in MUE dogs is prognostically relevant.

Ependymal and periventricular magnetic resonance imaging changes in four dogs with central nervous system blastomycosis.

Rapid detection of central nervous system (CNS) involvement is important for dogs with blastomycosis, as this can affect antifungal drug selection and has been associated with an increased risk of death. Previous reports describing magnetic resonance imaging (MRI) characteristics of canine CNS blastomycosis primarily identified mass lesions. The purpose of this retrospective study was to determine whether other MRI characteristics of CNS blastomycosis may also occur. Medical records of the Purdue University Veterinary Teaching Hospital were searched and four dogs met inclusion criteria. Magnetic resonance imaging characteristics included periventricular edema, periventricular and meningeal contrast enhancement, and ventriculomegaly. Periventricular lesions most commonly involved the rostral horn of the lateral ventricles and the third ventricle. Increased meningeal contrast enhancement involved the cerebrum, thalamus, sella turcica, and brainstem. Findings indicated that, in addition to mass lesions, MRI characteristics of periventricular hyperintensity, contrast enhancement, and ventriculomegaly may also occur in dogs with CNS blastomycosis.

Magnetic resonance imaging features of intracranial granular cell tumors in six dogs.

Magnetic resonance (MR) imaging characteristics of intracranial granular cell tumors (GCTs) have been previously reported in three dogs. The goal of this retrospective study was to examine a larger number of dogs and determine whether distinctive MR characteristics of intracranial GCTs could be identified. Six dogs with histologically confirmed intracranial GCTs and MR imaging were included. Tumor location, size, mass effect, T1- and T2-weighted signal intensity, and peritumoral edema MR characteristics were recorded. In all dogs, GCTs appeared as well-defined, extra-axial masses with a plaque-form, sessile distribution involving the meninges. All tumors were located along the convexity of the cerebrum, the falx cerebri, or the ventral floor of the cranial vault. All tumors were mildly hyperintense on T1-weighted images, and iso- to hyperintense on T2-weighted images. A moderate-to-severe degree of peritumoral edema and mass effect were evident in all dogs. Findings indicated that, while several MR imaging characteristics were consistently identified in canine cerebral GCTs, none of these characteristics were unique or distinctive for this tumor type alone.

Establishment and characterization of two novel patient-derived lines from canine high-grade glioma.

High-grade glioma is an aggressive cancer that occurs naturally in pet dogs. Canine high-grade glioma (cHGG) is treated with radiation, chemotherapy or surgery, but has no curative treatment. Within the past eight years, there have been advances in our imaging and histopathology standards as well as genetic charactereization of cHGG. However, there are only three cHGG cell lines publicly available, all of which were derived from astrocytoma and established using methods involving expansion of tumour cells in vitro on plastic dishes. In order to provide more clinically relevant cell lines for studying cHGG in vitro, the goal of this study was to establish cHGG patient-derived lines, whereby cancer cells are expanded in vivo by injecting cells into immunocompromized laboratory mice. The cells are then harvested from mice and used for in vitro studies. This method is the standard in the human field and has been shown to minimize the acquisition of genetic alterations and gene expression changes from the original tumour. Through a multi-institutional collaboration, we describe our methods for establishing two novel cHGG patient-derived lines, Boo-HA and Mo-HO, from a high-grade astrocytoma and a high-grade oligodendroglioma, respectively. We compare our novel lines to G06-A, J3T-Bg, and SDT-3G (traditional cHGG cell lines) in terms of proliferation and sensitivity to radiation. We also perform whole genome sequencing and identify an NF1 truncating mutation in Mo-HO. We report the characterization and availability of these novel patient-derived lines for use by the veterinary community.

Establishing an academic neurology specialty program: experiences over a five-year period.

Veterinary neurology is an expanding specialty field. At the time of this writing, 13 out of 33 (40%) US and Canadian veterinary colleges, and many more veterinary colleges outside of North America, had no active clinical neurology service. New academic programs will likely be established to fill this need, often starting with a single neurologist. Establishing a neurology service with one founding faculty member can be accomplished by developing the program in phases and creating a support network that optimizes faculty strengths and interests. Such an approach allows for the gradual expansion of services and staffing in a manageable way to ultimately provide a full-service program. A description of this development process at Purdue University School of Veterinary Medicine is presented as a case study and model for the establishment of other neurology or specialty services.

Application of magnetically actuated self-clearing catheter for rapid in situ blood clot clearance in hemorrhagic stroke treatment.

Maintaining the patency of indwelling drainage devices is critical in preventing further complications following an intraventricular hemorrhage (IVH) and other chronic disease management. Surgeons often use drainage devices to remove blood and cerebrospinal fluid but these catheters frequently become occluded with hematoma. Using an implantable magnetic microactuator, we created a self-clearing catheter that can generate large enough forces to break down obstructive blood clots by applying time-varying magnetic fields. In a blood-circulating model, our self-clearing catheters demonstrated a > 7x longer functionality than traditional catheters (211 vs. 27 min) and maintained a low pressure for longer periods (239 vs. 79 min). Using a porcine IVH model, the self-clearing catheters showed a greater survival rate than control catheters (86% vs. 0%) over the course of 6 weeks. The treated animals also had significantly smaller ventricle sizes 1 week after implantation compared to the control animals with traditional catheters. Our results suggest that these magnetic microactuator-embedded smart catheters can expedite the removal of blood from the ventricles and potentially improve the outcomes of critical patients suffering from often deadly IVH.

Case Report: Suspected Solitary Osseous Plasmacytoma in a Cat: Use of Magnetic Resonance Imaging to Diagnose and Confirm Resolution of Disease Following Chemotherapy.

A 9-year-old female spayed Domestic Shorthair cat presented for pain, reluctance to jump, and hyporexia of 14 days duration. Neurologic examination was consistent with C6-T2 myelopathy. Magnetic resonance imaging (MRI) revealed a solitary, contrast-enhancing lesion within the T2 vertebral body. Solitary osseous plasmacytoma was diagnosed based on neurologic examination, advanced imaging, and clinicopathologic findings. Melphalan and prednisolone therapy were initiated. Complete resolution of clinical signs and the vertebral lesion were documented at a 2-year follow up examination with neurologic examination and repeat spinal MRI, respectively. Solitary osseous plasmacytoma are rare neoplasms in humans and domestic animals. As such, there is a paucity of published information regarding diagnostic criteria, MRI findings, treatment modalities, progression, and remission of disease in the feline patient. Most data are extrapolated from human medicine. The purpose of this report is to document neurologic exam and MR findings at the time of diagnosis and complete resolution of a solitary osseous vertebral plasmacytoma following melphalan and prednisolone therapy.

Development of an In Vitro Hemorrhagic Hydrocephalus Model for Functional Evaluation of Magnetic Microactuators Against Shunt Obstructions.

OBJECTIVE: Occlusion of ventriculoperitoneal shunts placed after intraventricular hemorrhage occurs frequently. The objective of this study was to develop a hemorrhagic hydrocephalus model to assess the ability of an oscillating microactuator within the ventricular catheter (VC) to prevent shunt obstruction. METHODS: An in vitro hydrocephalus model with extreme risk of shunt obstruction was created. Phosphate-buffered saline, blood, and thrombin were driven through ventriculoperitoneal shunts for 8 hours. Five VCs were fitted with a microactuator and compared with 5 control VCs. The microactuator was actuated by an external magnetic field for 30 minutes. Pressure within the imitation lateral ventricle was measured. RESULTS: In the 5 control shunts, 6 obstructions developed (3 VC, 3 valve-distal catheter) compared with 1 obstruction (VC) in the 5 microactuator shunts. In the control and microactuator groups, the median volume exiting the shunts in 8 hours was 30 mL versus 256 mL. Median time to reach an intraventricular pressure of 40 mm Hg (13.8 minutes vs. >8 hours), median total time >40 mm Hg (6.2 hours vs. 0.0 hours), and median maximum pressure (192 mm Hg vs. 36 mm Hg) were significantly improved in the microactuator group (P < 0.01). CONCLUSIONS: In addition to protecting the VC, the microactuator appeared to prevent hematoma obstructing the valve or distal catheter, resulting in a much longer duration of low intraventricular pressures. A microactuator activated by placing the patient's head in an external magnetic field could reduce shunt obstructions in hemorrhagic hydrocephalus.

Cerebrospinal Fluid Drop Metastases of Canine Glioma: Magnetic Resonance Imaging Classification.

Dissemination of glioma in humans can occur as leptomeningeal nodules, diffuse leptomeningeal lesions, or ependymal lesions. Cerebrospinal fluid (CSF) drop metastasis of glioma is not well-recognized in dogs. Ten dogs with at least two anatomically distinct and histologically confirmed foci of glioma were included in this study. The 10 dogs underwent 28 magnetic resonance imaging (MRI) examinations, with distant CSF drop metastasis revealed in 13 MRIs. The CSF drop metastases appeared as leptomeningeal nodules in four dogs, diffuse leptomeningeal lesions in six dogs, and ependymal lesions in seven dogs; six dogs had a combination of lesion types. Primary tumors were generally T2-heterogeneous and contrast-enhancing. Many metastases were T2-homogeneous and non-enhancing. Diffuse leptomeningeal lesions were seen as widespread extra-axial contrast-enhancement, again very dissimilar to the intra-axial primary mass. Primary masses were rostrotentorial, whereas metastases generally occurred in the direction of CSF flow, in ventricles, CSF cisterns, and the central canal or leptomeninges of the cervical or thoracolumbar spinal cord. Seven of the dogs had received therapy limited to the primary mass, such as surgery or stereotactic radiation, then developed metastasis in the following months. CSF drop metastasis of glioma may take a very different appearance on MRI to the primary mass, including periventricular lesions that are more homogeneous and less contrast-enhancing, rostral horn signal changes, or leptomeningeal enhancement ventral to the brainstem or encircling the spinal cord.