TOMY OF THE CANINE BRAIN USING HIGH RESOLUTION OMPUTED TOMOGRAPHY*

High resolution computed tomography (CT) was used to determine the normal appearance of the brain of an adult Beagle dog. Objects as small as 0.6 mm for bony structures (high contrast) and 1.5–2.0 mm for soft tissue structures (low contrast) could be resolved in the CT images. Multiplanar imaging using direct transverse and reformatted dorsal and sagittal images made it possible to obtain a three dimensional presentation of anatomy. Selective viewing, where CT number window and level settings were varied, was used to optimize visualization of specific brain structures. Normal high contrast components, cerebrospinal fluid, and osseous land-marks, were important aids in identification of various intracranial structures. Quantitative densitometry was performed to characterize various regions of the brain in terms of their x-ray attenuation values or CT numbers. This study indicated that high resolution CT provides a qualitative and quantitative appraisal of the canine brain that is unavailable using conventional radiographic technics.     

Magnetic resonance imaging features of feline intracranial neoplasia: retrospective analysis of 46 cats

The purpose of this retrospective study was to determine the magnetic resonance imaging (MRI) characteristics of feline brain tumors and to determine whether these characteristics can be used to accurately predict the histologic diagnosis. MRI scans of 46 cats with histologically confirmed brain tumors were reviewed, including 33 meningiomas, 6 lymphomas, 4 gliomas, 2 olfactory neuroblastomas, and 1 pituitary tumor. MRI features including axial origin, shape, location, signal intensity, contrast enhancement, peritumoral edema, and mass effect were reviewed and characterized for each tumor type. Tumor shape, axial origin, contrast enhancement, and degree of peritumoral edema aided in the identification of tumor type. Meningiomas were always extra-axial and were most often ovoid with marked contrast enhancement and mild peritumoral edema. Gliomas were always intra-axial with ring enhancement and generally caused more peritumoral edema than other tumors. The brain tumor was detected on MRI in 45 (98%) cats. Two blinded independent reviewers correctly identified 82% of all of the tumor types on the basis of MRI appearance alone. Thus, MRI is an excellent diagnostic tool for the detection of brain tumors in cats, and it provides important information to aid in the diagnosis of tumor type.     

P40 polyester sheet plastination technique for brain and body slices: The vertical and horizontal flat chamber methods

The P40 technique produces high‐quality brain and body slices and is the user‐friendliest of the polyester techniques. The P40 polyester technique follows the same classical steps for plastination. That is, preparation of the specimen, fixation (optional), dehydration by freeze substitution, forced impregnation and curing. Two methods used to prepare two different types of specimens, that is, brain slices and body slices are described. Each method has its own characteristics depending on the specimen type used. Brain slices were used to illustrate the vertical small chamber method while the body slices were used to illustrate the horizontal large chamber method. The brain slices obtained using P40 are of very good quality presenting good contrast between grey and white matter. The body slices are also of very good quality. The physical appearance of these slices makes them an exceptional instrument for diagnostic imaging and anatomical correlation. Body slices prepared with P40 retain the natural colour of the tissue and preserve the anatomical relationships.     

Diagnostic utility of computed tomography imaging in equine intracranial conditions

Reasons for performing study: The use of computer tomography (CT) and contrast‐enhanced CT (CCT) to image the head is common. However, the validity of CT as a neurodiagnostic indicator of intracranial diseases in horses is unknown. Objective: To define the validity of CT and CCT in horses with suspected intracranial disorders. Methods: The validity of CT imaging was estimated by comparing clinical, clinicopathological and histopathological findings to CT findings in 15 horses presented for intracranial disorders, for which pre‐ and post contrast CT images and post mortem examination of the brain and skull were reviewed. Post mortem examination (gross and histopathological examination) was considered as the gold standard; and sensitivity, specificity, predictive values, likelihood ratios, and pre‐ and post test probabilities were calculated. Results: All horses had abnormal neurological examinations on admission. Computer tomography imaging identified intracranial lesions in 8 horses, and included masses (oligodendroglioma, adenocarcinoma and cholesterinic granulomas), acute haemorrhage and skull fractures. Computer tomography imaging failed to identify intracranial lesions in 6 cases, which included meningitis, meningoencephalitis and nonacute haemorrhage. Lesions not recognised by CT were also not evident on gross examination but were identified by histopathological examination of the brain. Post mortem examination of the brain and skull was unremarkable in one horse, for which cranial CT imaging was normal (specificity, 100%). Therefore, the odds of having an intracranial lesion after an abnormal CT were very high. In contrast, there was a moderate sensitivity (57.1%, 95% confidence interval: 29.6–81.2). Conclusions and potential relevance: CT was an excellent neurodiagnostic tool in identifying skull fractures, intracranial space‐occupying lesions (e.g. neoplasia) and acute haemorrhage and allows to rule in intracranial disorders. However, CT showed limited sensitivity in identifying inflammatory disorders and small parenchymal lesions in the equine brain, which was not further detectable after contrast administration.     

INVITED REVIEW—NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

The evaluation of therapeutic response using cross‐sectional imaging techniques, particularly gadolinium‐enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the response evaluation criteria in solid tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging‐based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and response assessment in neuro‐oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment‐induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy‐induced changes. Finally, although objective endpoints such as MR imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria.     

Possibilities for computer tomography of the equine head based on two cases with a fracture of the base of the skull]

For the past 2 years computed tomography is used at the Veterinary School, University of Zürich. This new imaging modality enables the detection of abnormalities occurring in small and large animals which were previously not visible with imaging techniques. Subjects of this study were a foal and a small pony, both with suspected head trauma. Routine radiography could not explain any of the neurological deficiencies. In the first case a basilar skull fracture along with a focal brain hemorrhage was detected, in the second case multiple basilar skull fractures were seen. The computed tomographic examination after intravenous injection of an iodine-containing contrast medium also revealed epidural hemorrhage. These two cases demonstrate the diagnostic use of computed tomography as an extremely valuable asset when diagnosing head trauma in horses.     

Magnetic resonance imaging findings in histologically confirmed Pug dog encephalitis

The purpose of the study was to describe magnetic resonance (MR) imaging features of histologically confirmed necrotizing encephalitis in four Pugs and to compare those findings with MR imaging characteristics of necrotizing encephalitis in other breeds. All dogs had the following common findings: lesions restricted to the forebrain, both cerebral hemispheres diffusely but asymmetrically affected, lesions affected gray and white matter resulting in loss of distinction between both, most severe lesions in occipital and parietal lobes, lesions were irregularly T2-hyperintense and T1-isointense to slightly T1-hypointense, and no cavitation. There were various degrees of contrast enhancement of brain and leptomeninges. Asymmetry of lateral ventricles and midline shift was seen in one dog each. Two dogs had brain herniation, which may have contributed to the progression of neurologic signs. Hyperintensity on T2-weighted and fluid attenuated inversion recovery images in the hippocampus and piriform lobe was consistent with excitotoxic edema, whereas similar imaging features in other forebrain areas corresponded to areas of inflammation or liquefaction on histopathology. In comparison with necrotizing encephalitis in other canine breeds, Pug dog encephalitis has some unique MR imaging features. Therefore, these characteristics cannot be applied to other breeds, nor should imaging features of necrotizing encephalitis of other canine breeds be used for interpretation of MR images in Pug dogs.     

Magnetic resonance imaging findings in acute canine distemper virus infection

Demyelination is the prominent histopathological hallmark in the acute stage of canine distemper virus infection. Magnetic resonance imaging is an important diagnostic tool in human beings to determine demyelination in the brain, for example in multiple sclerosis. Five young dogs with clinically suspected canine distemper virus infection were subjected to magnetic resonance imaging of the brain and histopathological and immunohistochemical examinations. Hyperintense lesions and loss of contrast between grey and white matter were detected in T2-weighted images in the cerebellum and/or in the brainstem of three dogs, which correlated with demyelination demonstrated in histopathological examination. Furthermore, increased signal intensities in T2-weighted images were seen in the temporal lobe of four dogs with no evidence of demyelination. Magnetic resonance imaging seems to be a sensitive tool for the visualisation of in vivo myelination defects in dogs with acute canine distemper virus infection. Postictal oedema and accumulation of antigen positive cells have to be considered an important differential diagnosis.     

EFFECT OF DELAYED ACQUISITION TIMES ON GADOLINIUM‐ENHANCED MAGNETIC RESONANCE IMAGING OF THE PRESUMABLY NORMAL CANINE BRAIN

A delay in imaging following intravenous contrast medium administration has been recommended to reduce misdiagnoses. However, the normal variation of contrast enhancement in dogs following a delay has not been characterized. Contrast‐enhanced MR imaging of 22 dogs was assessed, in terms of identification of normal anatomic structures, to investigate the variation associated with 10‐min delay between contrast medium administration and imaging. All dogs had a normal brain MR imaging study and unremarkable cerebrospinal fluid. Specific regions of interest were assessed both objectively, using computer software, and subjectively using three observers. Mean contrast enhancement >10% was seen in the pituitary gland, choroid plexus, meninges, temporal muscle, trigeminal nerve, and the trigeminal nerve root. Structures with an active blood–brain barrier had minimal contrast enhancement (<6%). Enhancing structures had significantly more contrast enhancement at t=1 min vs. t=10 min, except in temporal muscle, the trigeminal nerve and the trigeminal nerve root. Interobserver agreement was moderate to good in favor of the initial postcontrast T1‐weighted (T1w) sequence. The observers found either no difference or poor agreement in identification of the nonvascular structures. Intraobserver agreement was very good with all vascular structures and most nonvascular structures. A degree of meningeal enhancement was a consistent finding. The initial acquisition had higher enhancement characteristics and observer agreement for some structures; however, contrast‐to‐noise was comparable in the delayed phase or not significantly different. We provide baseline references and suggest that the initial T1w postcontrast sequence is preferable but not essential should a delayed postcontrast T1w sequence be performed.     

A BOLD-fMRI study of cerebral activation induced by injection of algesic chemical substances into the anesthetized rat forepaw

This study was performed to examine whether the brain activities induced by noxious algesic chemical substances in anesthetized animals could be detected by blood oxygen-level-dependent functional magnetic resonance imaging (BOLD-fMRI). Multislice gradient echo images of the primary somatosensory cortex were obtained using a 7.05 T superconducting system and a one-turned surface coil centered over the primary somatosensory cortex of the 1.0%-isoflurane-anesthetized rat. The Z-score t-map of BOLD signals and its time-course analysis revealed that subcutaneous injection of formalin into the left forepaw immediately induced an early response in the contralateral primary sensory cortex lasting for a few minutes, followed by a late response until 20 min after stimulation. In contrast, injection of capsaicin into the left forepaw evoked only the early response. Furthermore, pretreatment with morphine completely abolished these responses induced by the chemical algesic substances. Thus BOLD-fMRI is a useful method to analyze the brain activities of painful stimulation in anesthetized animals.     

Imaging diagnosis--lack of contrast enhancement in metastatic cerebral adenocarcinoma

A 7-year-old female spayed Scottish Terrier was presented with central nervous system symptoms suggestive of a lesion in the forebrain. Magnetic resonance (MR) imaging revealed multifocal disease in the forebrain. Because of complete lack of contrast enhancement, the changes were attributed to lesions of inflammatory origin. Histopathology of the brain revealed multiple metastatic lesions of an adenocarcinoma. Brain metastases in general show contrast enhancement. The reason for a complete absence of contrast enhancement is unknown. Previous administration of corticosteroids, increased diffusion time of contrast medium, increased intracranial pressure in combination with an intact blood-tumor barrier is discussed as possible reasons.     

A REVIEW OF NONCONVENTIONAL ULTRASOUND TECHNIQUES AND CONTRAST-ENHANCED ULTRASONOGRAPHY OF NONCARDIAC CANINE DISORDERS

Modern ultrasound contrast media are gas-containing stabilized microbubbles that remain intact in the circulating blood for several minutes after intravenous injection and increase the intensity of the backscattered ultrasound. When the microbubbles disappear from the blood, they can be detected in the parenchyma of the liver and the spleen for about 30 more minutes (late liver- and spleen-specific phase). The insonated microbubbles produce second harmonic ultrasound frequencies, whose detection requires nonconventional ultrasound modalities such as pulsed inversion imaging. Nonconventional ultrasound techniques can also be used without microbubbles because second harmonics can be generated by ultrasound in tissues as well. The physical principles and advantages of nonconventional ultrasound techniques are described. The circulating microbubbles can be used not only to enhance weak Doppler signals, but also to perform dynamic contrast studies. Contrast-enhanced dynamic ultrasound studies--similar to contrast-enhanced CT and MRI examinations--have been used in humans to characterize lesions noninvasively (i.e., without biopsies) found during conventional ultrasound examinations. To map the distribution of contrast medium in a nodule or in an organ, specific scanning techniques such as stimulated acoustic emission have been developed. Stimulated acoustic emission occurs when high acoustic pressure ultrasonic waves disrupt the stationary or slowly moving microbubbles. This results in the release of a large amount of harmonic ultrasound frequencies. When the stimulated acoustic emission technique is used for dynamic studies, scanning must be interrupted several times to allow the microvasculature of the lesion to refill with microbubbles (interval delay imaging). The contrast patterns of malignant and benign hepatic nodules in humans have been the most intensively studied. Another type of dynamic study in humans measures the transit time of the contrast medium; that is, how fast the peripherally injected microbubbles reach the hepatic veins. Hepatic cirrhosis can be differentiated from other diffuse parenchymal liver diseases by a shorter transit time. Introducing nonconventional ultrasound techniques and ultrasound contrast media in veterinary diagnostic imaging may have potential value; however, intensive research should be carried out before ultrasound contrast agents can routinely be used in clinical practice.     

Diagnostic correlation of CT-MRI and histopathology in 10 dogs with brain neoplasms

Ten dogs with primary (n = 8) and metastatic (n = 2) brain tumours were studied in an attempt to evaluate the diagnostic sensitivity of computed tomography (CT) or magnetic resonance imaging (MRI). Of the clinical signs noticed, seizures (seven of 10), behavioural abnormalities and cognition dysfunction (seven of 10), compulsive walking and circling (six of 10), sensorimotor (five of 10) and neuro-opthalmological (two of 10) dysfunction were the most common. In all 10 animals that finally died of the disease or were killed, the histopathological diagnosis that followed necropsy was taken as a golden standard in the CT or MRI prediction of the histological type of brain neoplasms. In every instance, tumour detection, morphology and histological differentiation were possible with the aid of either CT (seven of 10) or MRI (three of 10) imaging especially after contrast enhancement. Only one CT-evaluated dog, diagnosed as meningioma, was found to be astrocytoma on histopathology. Interestingly, a rare case of cerebellar medulloblastoma was correctly identified in MRI scans.     

Contrast-enhanced magnetic resonance angiography (CE-MRA) of intra- and extra-cranial vessels in dogs

Until recently intra- and extra-cranial vessels in dogs have been imaged using conventional X-ray or digital subtraction angiography. As both of these methods are surgically demanding and involve the use of complex equipment with potential risks for the animal, they are now mainly used in experimental work. In this study, a method for delineating the intra- and extra-cranial vessels of dogs using contrast-enhanced magnetic resonance angiography (CE-MRA) has been examined. The MR images were acquired on a 1.5-T scanner after a bolus injection of gadolinium contrast medium. CE-MRA showed most of the major intra- and extra-cranial arteries and veins as well as most venous sinuses and plexuses of the brain. Difficulties may arise in differentiating between minor arterial and venous vessels as well as in the measurement of vessel diameter. More frequent use of this diagnostic method in clinical cases will indicate whether MRA of the head and brain is of as much use in veterinary medicine as it has become in human medicine. There is certainly potential value in detecting rare conditions in animals such as aneurysms and vascular malformations, as well as in examining vessels feeding intracranial masses and the investigation of cerebrovascular accidents.     

MAGNETIC RESONANCE IMAGING OF THE CANINE BRAIN AT 7 T

The purpose of this study was to describe relevant canine brain structures as seen on T2-weighted images following magnetic resonance (MR) imaging at 7 T and to compare the results with imaging at 1.5 T. Imaging was performed on five healthy laboratory beagle dogs using 1.5 and 7 T clinical scanners. At 1.5 T, spin echo images were acquired, while gradient echo images were acquired at 3 T. Image quality and conspicuity of anatomic structures were evaluated qualitatively by direct comparison of the images obtained from the two different magnetic fields. The signal-to-nose ratio (SNR) and contrast-to-noise ratio (CNR) were calculated and compared between 1.5 and 7 T. The T2-weighted images at 7 T provided good spatial and contrast resolution for the identification of clinically relevant brain anatomy; these images provided better delineation and conspicuity of the brain stem and cerebellar structures, which were difficult to unequivocally identify at 1.5 T. However, frontal and parietal lobe and the trigeminal nerve were difficult to identify at 7 T due to susceptibility artifact. The SNR and CNR of the images at 7 T were significantly increased up to 318% and 715% compared with the 1.5 T images. If some disadvantages of 7 T imaging, such as susceptibility artifacts, technical difficulties, and high cost, can be improved, 7 T clinical MR imaging could provide a good experimental and diagnostic tool for the evaluation of canine brain disorders.     

AN OPTIMIZED PROTOCOL FOR MULTISLICE COMPUTED TOMOGRAPHY OF THE CANINE BRAIN

Computed tomography (CT) is commonly used in veterinary practice to evaluate dogs with suspected brain disease, however contrast resolution limitations and artifacts may reduce visualization of clinically important anatomic features. The purpose of this study was to develop an optimized CT protocol for evaluating the canine brain. The head of a 5‐year‐old Springer Spaniel with no neurological signs was imaged immediately following euthanasia using a 4‐slice CT scanner and 282 protocols. Each protocol used a fixed tube voltage of 120 kVp and 10 cm display field of view. Other acquisition and reconstruction parameters were varied. For each protocol, four selected images of the brain were reconstructed, anonymized and saved in DICOM format. Three board‐certified veterinary radiologists independently reviewed each of the four images for each protocol and recorded a numerical quality score for each image. The protocol yielding the lowest total numerical score was defined as the optimal protocol. There was overall agreement that the optimal protocol was the one with the following parameters: sequential mode, 300 mAs, 1 mm slice thickness, 1 s tube rotation time, medium image reconstruction algorithm and applied beam hardening correction. Sequential imaging provided optimal image resolution. The thin‐sliced images provided a small blur due to partial volume artifacts. A high tube current resulted in a relatively low noise level. Use of a medium frequency image reconstruction algorithm provided optimal contrast resolution for brain tissue. Use of a proprietary beam hardening correction filter (Posterior Fossa Optimization) markedly reduced beam‐hardening artifact.     

Contrast-enhanced fluid-attenuated inversion recovery vs. contrast-enhanced spin echo T1-weighted brain imaging

In humans, contrast-enhanced fluid-attenuated inversion recovery (FLAIR) imaging plays an important role in detecting brain disease. The aim of this study was to define the clinical utility of contrast-enhanced FLAIR imaging by comparing the results with those with contrast-enhanced spin echo T1-weighted images (SE T1WI) in animals with different brain disorders. Forty-one dogs and five cats with a clinical suspicion of brain disease and 30 normal animals (25 dogs and five cats) were evaluated using a 0.2 T permanent magnet. Before contrast medium injection, spin echo T1-weighted, SE T1WI, and FLAIR sequences were acquired in three planes. SE T1WI and FLAIR images were also acquired after gadolinium injection. Sensitivity in detecting the number, location, margin, and enhancement pattern and rate were evaluated. No lesions were found in a normal animal. In affected animals, 48 lesions in 34 patients were detected in contrast-enhanced SE T1WI whereas 81 lesions in 44 patients were detected in contrast-enhanced FLAIR images. There was no difference in the characteristics of the margins or enhancement pattern of the detected lesions. The objective enhancement rate, the mean value between lesion-to-white matter ratio and lesion-to-gray matter ratio, although representing an overlap of T1 and T2 effects and not pure contrast medium shortening of T1 relaxation, was better in contrast-enhanced FLAIR images. These results suggest a superiority of contrast-enhanced FLAIR images as compared with contrast-enhanced SE T1WI in detecting enhancing brain lesions.     

USE OF [123I]-2-IODO-l-PHENYLALANINE AS A TUMOR IMAGING AGENT IN TWO DOGS WITH SYNOVIAL CELL SARCOMA

[123I]-iodo-L-phenylalanine was successfully evaluated for gamma camera imaging in vivo in tumor-bearing athymic mice and in humans with brain tumors. Here, we report the use of this tracer in two dogs with synovial cell sarcoma of the tarsus. [123I]-iodo-L-phenylalanine was quantitatively prepared as a kit formulation using the Cu(1+) +-assisted nucleophilic exchange. Rapid [123I]-2-iodo-L-phenylalanine tumor accumulation was observed with good tumor to background contrast and rapid clearance in these two dogs. This radiopharmaceutical is a promising alternative tumor tracer to overcome the known limitations of 18F-fluorodeoxyglucose and, when labelled with radioiodine-131, has the potential to be used for therapeutic purposes.