Magnetic Resonance Imaging

The physics of MRI has been described in numerous publications and details can be found elsewhere.²¹ Briefly, MRI involves placing a patient in a scanner that has a large magnet. The protons (hydrogen nuclei) that are found in water molecules in the body align themselves with the magnetic field. Another electromagnetic field oscillates at specific radiofrequencies perpendicular to the main magnetic field, which pushes some of the protons out of alignment with the main magnetic field. As these protons return to their normal alignment with the main magnetic field, they emit a radiofrequency signal that is detected by a receiver. Protons in different tissue types throughout the body realign at different speeds. A computer analyzes these differences, and images are created based on the location and speed of realignment.²¹

Several MRI pulse sequences are performed routinely that take advantage of natural physical characteristics of tissues to highlight different features. The most common sequences utilized are T2-weighted images (T2WI), precontrast and postcontrast T1-weighted images (T1WI), and fluid-attenuated inversion recovery (FLAIR) images. Fluid is hyperintense (bright) on T2WI; therefore cerebrospinal fluid (CSF) in the ventricular system is white. This pulse sequence is excellent for detection of pathology, because many CNS diseases will lead to increased fluid in the brain, either via intracellular fluid from cells (e.g., inflammatory or neoplastic cells) or from edema. The delineation between gray and white matter is clearly identifiable on T2WI. Fluid is hypointense (dark) on T1WI, so CSF in the ventricular system is black. Precontrast T1WI studies are performed to evaluate the brain for normal anatomical structures and to compare with T1WI images obtained after administration of contrast agent (gadolinium), which appears as a hyperintense (white) signal on postcontrast T1WI. Contrast enhancement indicates breakdown in the blood-brain barrier (BBB). Possible causes include neoplasia, inflammatory disease, infection, vasculitis, and hemorrhage. Several areas within the brain contrast enhance routinely because of high vascularity and/or lack of BBB. These include the meninges (mild), pituitary gland, choroid plexus, and pineal gland. The FLAIR sequence is used primarily for detection of pathology in periventricular regions and near the surface of the brain. FLAIR images are T2WI in which the signal for “pure” fluids (e.g., CSF) is suppressed. As a result CSF is black on FLAIR image, whereas impure fluids such as cerebral edema remain hyperintense and are detected more easily in the periventricular and subarachnoid regions where they can be overlooked on T2WI.

MRI is the imaging modality of choice for detection of CNS lesions in human patients. The sensitivity for detection of brain tumors has been shown to be 98 to 99 per cent for human beings, dogs, and cats.^22–24 MRI provides superior resolution of intracranial lesions compared with CT, and is more sensitive for detection of primary and secondary brain tumors, infarction, white matter diseases, subacute to chronic hemorrhage, and neurodegenerative diseases.²⁵ Advantages of MRI over CT include the ability to produce high resolution images of soft-tissue structures, the acquisition of images in multiple planes without having to move the patient, lack of ionizing radiation, the ability to visualize edema easily, and lack of “beam-hardening” artifacts surrounding the brainstem and cerebellum that can obscure small lesions.^21,25 Relative disadvantages compared with CT include increased cost, lower sensitivity in identifying bone lesions, calcification, acute hemorrhage, and longer scan time.^21,25

MRI features of individual brain tumors have been described for several tumor types and will be discussed in additional detail below. Findings that appear to aid in the differentiation of neoplastic from nonneoplastic lesions include single lesion, regular shape (spheroid or ovoid), contact with the meninges, presence of a dural tail (extension of hyperintense signal or contrast enhancement along the meninges beyond the boundary of the lesion), lesions that affect the adjacent bone, and the presence of contrast enhancement.²⁶

Computed Tomography

Computed tomographic images essentially are cross-sectional “slices” of the body utilizing x-ray technology. However, photon detection is much higher with CT compared with conventional radiographs; therefore slight differences in attenuation lead to improved contrast resolution.* Advantages of CT compared with MRI include shorter scan times; higher sensitivity for detection of bone lesions, calcification, and acute hemorrhage; and reduced cost.^21,29 Disadvantages compared with MRI include exposure of the patient to large doses of radiation; decreased sensitivity for soft tissue structures; presence of bone artifacts created by thick bone surrounding the caudal fossa (brainstem and cerebellum), which can lead to inability to visualize lesions; and inability to easily obtain images in all planes without moving the patient.^21,29 Description of CT features of large numbers of feline brain tumors primarily has been limited to meningioma,^{13,14,28,30,31} but small case series or case reports have described the use of CT for pituitary tumors,^32–34 lymphoma,^35–37 ependymoma,³⁸ intracerebral plasma cell tumor,³⁹ and middle-ear tumors extending into the brainstem.⁴⁰

Cerebrospinal Fluid Analysis

CSF analysis rarely provides a definitive diagnosis for brain tumor.^16,43 It is used to aid in the diagnosis of CNS disease, but may not be necessary based on results of MRI or CT imaging.⁶ In general, CSF collection is very safe. However, space-occupying masses can lead to increased intracranial pressure (ICP), and the subsequent alteration of ICP with CSF drainage may lead to brain herniation.²² CSF collection should be performed after imaging whenever possible to evaluate potential risks versus benefits.⁶

CSF analysis is very sensitive for identification of CNS disease, but is not specific to etiology with the exception of the occasional detection of lymphoblasts with CNS lymphoma (Figure 55-1), rare identification of tumor cells on CSF cytology, and identification of infectious organisms (e.g., Cryptococcus neoformans).^5,37,43,44 There is a wide range of reported CSF results for various tumor types.^† For example, one study found normal CSF in 3 of 10 cats with meningioma.¹⁷ CSF analysis was performed in 28 cats in a retrospective study of 160 cats with brain tumors. The median total protein was 38 mg/dL (range, 16 to 427; normal, <25) and the median nucleated cell count was 5 cells/µL (range, 0 to 162; normal, <5).⁵ Similar findings were reported in a retrospective study of CSF analyses of cats with noninflammatory CNS disease.⁴⁴ Albuminocytologic dissociation (increased total protein without a concomitant increase in nucleated cell count) has been reported to occur with intracranial neoplasia. This abnormality was identified in eight (28.6 per cent) cats.⁵ However, albuminocytologic dissociation has been reported with other CNS disorders, including noninflammatory degeneration with tissue necrosis, vascular lesions with hemorrhage, and certain types of viral encephalitis.⁴³

Figure 55-1 Cerebrospinal fluid obtained from a 4-year-old neutered male cat with a 2-week history of ataxia and seizures. Cytological examination revealed a lymphocytic pleocytosis characterized by a large number of lymphoblasts.

Skull Radiographs

In general, skull radiographs have limited value in the diagnosis of brain tumors, but may be of some assistance if advanced imaging is not available or cost-prohibitive to the owner. Routine views should include lateral and ventrodorsal (VD) or dorsoventral (DV) views. The closed-mouth VD view is best for evaluation of the frontal and prefrontal regions, whereas the open-mouthed VD view is best for evaluation of the nasal cavity. Open-mouth frontal view is best for evaluation of the foramen magnum and cerebellar region.²⁷ Dorsoventral and right and left oblique DV views can be used to evaluate the tympanic bullae to rule out otitis media and ear tumors (see Chapter 31).^15,27 Meningiomas lead frequently to thickening of the overlying calvaria (hyperostosis) that can be detected on skull radiographs, as well as with CT and MRI.^5,17,28 Varying degrees of calcification within the tumor, enlargement of the middle meningeal artery, and rare invasion of the calvaria with localized destruction of bone also may be detected on routine skull radiographs.¹⁷

Electroencephalography

Electroencephalography (EEG) is the recording of spontaneous electrical activity from the cerebral cortex via subcutaneous or surface electrodes. A study analyzing EEG results from 201 dogs and six cats thought to have space-occupying lesions found that EEG recordings from all of the patients had abnormalities in at least one lead. However, there was no correlation between the side of the brain affected on EEG and lesion location in the 27 dogs that underwent necropsy (none of the cats underwent necropsy). A major limitation of the study was that none of the patients appeared to undergo advanced imaging, and only a small proportion of the patients underwent necropsy.⁴⁷ Another smaller study of 10 cats with meningioma found that only 50 per cent of the cats had EEG abnormalities over the appropriate cerebral hemisphere. Two cats had normal EEG recordings, two cats had changes contralateral to lesion location, and one cat had abnormalities only on the right side despite a massive tumor distorting both sides of the brain. These studies suggest that EEG is sensitive for detecting a cerebral lesion, but not specific to lesion location.¹⁷

Ultrasound

Brain imaging with ultrasound is limited because of bone interference. However, it can be directed through an open fontanelle (primarily to diagnose hydrocephalus), or intraoperatively through a craniotomy window to assist with locating an intraparenchymal lesion and for ultrasound-guided biopsy.²⁷

Other Diagnostic Tests

Many other diagnostic tools have been described in the literature, including magnetic resonance spectroscopy,^27,48 electromyography (EMG),¹⁶ cerebral angiography,^16,27 cavernous sinus venography,^16,27 optic thecography,^16,27 scintigraphy,^16,27 and others. Many of these are performed infrequently because of the widespread availability and increased sensitivity of MRI and CT. Others (EMG) are performed uncommonly or are still in the early stages of use in veterinary neurology (MR spectroscopy).

Corticosteroids

Corticosteroids are the mainstay of symptomatic treatment.^6–915 They are used primarily to reduce peritumoral edema and decrease CSF production, both of which help to lower ICP, alleviating clinical signs temporarily. Prednisone or prednisolone is used most commonly. The typical dose is 0.5 mg/kg PO q12h for 1 to 2 weeks, followed by tapering to the lowest effective dose. Once daily dosing may be required long term to control clinical signs.

Anticonvulsants

Phenobarbital is the first-line anticonvulsant in cats and should be started if seizures occur. The standard starting dose is 1 to 2 mg/kg PO q12h.⁷ Serum phenobarbital levels should be measured 2 weeks after initiating treatment or after any change in dose. The “therapeutic range” is 15 to 40 µg/mL. Although hepatotoxicity appears to be less common in cats compared with dogs, many neurologists prefer not to exceed 35 µg/mL to decrease the risk of inducing liver damage. Phenobarbital induces synthesis and release of liver enzymes, particularly alkaline phosphatase (ALP). Bile acid assays should be performed every 6 months to differentiate hepatotoxicity from normal increases in liver enzyme values. Bile acid assays, and possibly abdominal ultrasound and liver biopsy, also should be performed when there are clinical signs of liver dysfunction, compatible blood value alterations (e.g., increased liver enzymes, decreased blood urea nitrogen, decreased cholesterol, decreased albumin), or increasing serum phenobarbital levels without increasing doses of phenobarbital.

Potassium bromide (KBr) can be used if needed; however, a recent study found that almost 40 per cent of cats developed a cough and had clinical and radiographic features similar to those seen in feline asthma. One of the cats was euthanized because of the severity of coughing.⁵⁰ Potassium bromide should be discontinued at the first sign of coughing in the feline patient.

Diazepam is a very effective anticonvulsant and at one time was the second choice for oral anticonvulsant therapy until several reports described acute, fulminant hepatic necrosis in some cats treated with oral diazepam.^51–53 Oral diazepam can be used, but with extreme caution. Serum liver enzymes should be monitored at 1 week and at 1 month after initiation of treatment.⁵⁴

A recent study evaluated levetiracetam (Keppra; 20 mg/kg PO q8h) as an adjunct to phenobarbital in a small group of cats with suspected idiopathic epilepsy. A good response (greater than 50 per cent reduction of seizures) was observed in seven of 10 cats. Side effects were transient and included lethargy and inappetence in two cats.⁵⁵ Limited information is available regarding other anticonvulsants; however, there is anecdotal use of zonisamide (Zonegran; 5 to 10 mg/kg PO q12h) in cats with seizures and it appears to be well tolerated. (See Chapter 54 for further discussion of novel anticonvulsant therapies.)

Surgery

Excision of meningioma and other tumors that are surgically accessible is considered the gold standard for definitive treatment and should be performed whenever possible.^7,15 Multiple studies have been published describing the surgical removal of meningioma in small case series, as well as individual case reports.^{5,13,14,17,30} In general, meningiomas (Figure 55-2) in cats are less invasive than in dogs and, as a result, they usually are easily excised.⁴⁹ Sporadic case reports describe surgical excision of lymphoma,³⁷ ependymoma,^38,56 medulloblastoma,^57,58 and aural tumors that extended into the brain.⁴⁰ A recent report also describes the technique of transsphenoidal hypophysectomy for removal of pituitary gland tumors.³⁴

Figure 55-2 Intraoperative photograph of a 12-year-old neutered male cat undergoing a left lateral rostrotentorial craniectomy. The cat’s nose is to the left. An extraaxial mass is visible through the cranial portion of the craniectomy window. Normal brain tissue is visible at the caudal end of the window. Histopathological examination confirmed the mass to be a meningioma. The cat survived 3 years before being euthanized for an unrelated illness.

Radiation Therapy

Along with surgical excision, radiation therapy (RT) can be an effective definitive treatment option for cats, and is becoming more widely available in veterinary medicine. Despite this, there are few reports describing its use in cats. Most of these reports describe use of RT in cats with pituitary tumors or intracranial lymphoma.^32,33,37,59 Typically RT consists of 15 to 20 fractions of radiation to the tumor, requiring a brief (10 to 15 minute) anesthetic procedure each time. Administration of photons or electrons via linear accelerator is the most common form of RT in veterinary medicine, but some institutions use Cobalt-60 gamma radiation. DNA is damaged by the radiation in the targeted tissue. When the tumor cells attempt to divide, they are unable to replicate themselves and undergo cell death. For tumors that are dividing rapidly, the tumor will shrink sooner and a clinical effect is seen more quickly, whereas slow-growing tumors may take up to 3 to 4 months before clinical benefit is noted. Oral corticosteroids are often started prior to RT to help alleviate clinical signs. In general, patients who do not respond to corticosteroids prior to starting RT may not be acceptable candidates for RT, because it may take too long to see the beneficial effects.

Most patients tolerate radiation treatment very well as long as there are no concurrent systemic medical diseases (e.g., heart murmur, diabetes mellitus). The most common side effect is radiation-induced inflammation in the brain; however, this usually resolves quickly with a short course of oral corticosteroids. Long-term adverse effects are uncommon because the natural remaining life span after diagnosis of a brain tumor usually is too short for long-term effects to occur.