Richard A. LeCouteur, BVSc, PhD, DACVIM (Neurology), DECVN
Department of Surgical & Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA
The detection, localization and characterization of brain lesions has been greatly improved through the use of computed tomography (CT) and magnetic resonance (MR) imaging. However, there remains a need to obtain an intra-operative neuro-pathological diagnosis from tissue samples of the lesion. The intra-operative cytological evaluation of smear preparations of brain lesions has become a routine procedure, providing a rapid, highly accurate diagnosis. In addition, future therapies may involve intra-lesional administration of drugs, following results of a brain biopsy. The need to obtain biopsy material for diagnosis and/or to deliver therapeutic agents with precision and without an invasive surgical procedure has stimulated the development and refinement of image-guided brain biopsy.
Neoplastic, vascular, infectious, or inflammatory diseases of dogs and cats frequently result in focal brain involvement. Although CT and MRI are sensitive in determining location, extent, and relationships to adjacent structures, of brain lesions, both have limited specificity. For example, non-neoplastic lesions (such as those seen in association with infectious, inflammatory, or vascular diseases) may mimic the CT or MRI appearance of a neoplasm. In most instances, results of CT or MRI provide only a broad list of differential diagnoses for a focal brain lesion. Accurate histologic diagnosis of an intracranial lesion is critical before recommending a specific management or treatment strategy.
CT-Guided Stereotactic Brain Biopsy
Brain biopsy should be approached with caution in animals with underlying coagulopathies, clinical signs consistent with increased intracranial pressure (ICP), animals with brainstem lesions, or systemic problems that result in increased anesthetic risk.
Equipment & Anesthetic Considerations
Essentially all closed stereotactic brain biopsy methods rely on the three-dimensional CT-generated coordinates identifying the lesion location. These coordinates are used to plot an optimal trajectory and depth needed for a biopsy needle to reach a target and obtain a diagnostic tissue sample.
Technical impediments exist to the direct application of most human stereotactic systems to dogs and cats. Most commercially available systems use a cumbersome head-frame and localizing system, designed specifically for the human skull, and require dedicated, expensive computer software for the planning phase. Several different systems for image-guided stereotactic brain biopsy have been reported for use in dogs and cats.
General anesthesia is required for stereotactic brain biopsy. Typically, premedication utilizes an opioid (a pure mu agonist because of using fentanyl in the maintenance phase). The dose and use of this drug will depend on the concern over changes in ICP and the mental status of the patient. Anesthesia usually is induced with propofol (± a benzodiazepine). Propofol (0.1–0.4 mg/kg/minute) and fentanyl (0.3–0.7 µg/kg/minute) are recommended for maintenance. . Animals should be ventilated to maintain ETCO2 at a value of 30–35 mm Hg. For recovery the fentanyl should be stopped about 30 minutes before the end of the procedure.
Two to three hours depending on the number of biopsy specimens collected and the number of trajectories planned.
Stereotactic biopsy begins with proper patient selection. The possibility of non-neoplastic disorders such as infection, cerebral infarction, or vasculitis, must be considered and investigated with other tests in appropriate patients prior to biopsy. When the differential diagnosis list is long and may include neoplasms and inflammatory lesions, the appropriate handling of tissue samples should be discussed with a neuropathologist in advance of the procedure. All patients should be tested for coagulation parameters (prothrombin time [PT], partial thromboplastin time [PTT]) prior to the procedure and should have a platelet count greater than 100,000. Patients should not receive aspirin products for 1 week before surgery. Ideally, MRI or CT images should be completed within five days prior to completion of the biopsy procedure.
Although stereotactic brain biopsy is minimally invasive (compared to open biopsy procedures), complications may occur. Morbidity may include seizures, hemorrhage, development of biopsy-induced neurologic deficits, brain infection, tumor seeding, and lack of definitive diagnosis.
Biopsy generally is done on the CT-scanner table. For those lesions not well identified on CT images, MRI images that demonstrate a lesion may be used to localize the lesion on CT images, using well-defined anatomic landmarks (e.g., lateral ventricles). Transverse CT images are used to define the CT coordinates of reference markers and the biopsy target. Dorsal or sagittal images may be used for trajectory planning. An entry point should be selected that is associated with a low risk for neurologic deficit or hemorrhage (e.g., avoidance of dorsal sagittal sinus). Ependymal puncture should be avoided where possible. A small craniotomy (2-mm diameter) is made by means of a twist drill, the dura mater is punctured with an 18-gauge needle, and biopsies may be done with a side-cutting aspirator biopsy needle (Nashold Biopsy Needle, Integra Radionics, Burlington MA) with a 10-mm side opening. On average, one to three specimens are harvested from each biopsy site.
The intraoperative goal should be to confirm by means of smear or touch preparations whether tissue satisfactory for an eventual diagnosis has been obtained. A specific histologic diagnosis may require routine formalin fixation and paraffin embedding of the biopsy tissue. At the conclusion of the biopsy procedure, the needle is withdrawn in increments to assess any possibility of hemorrhage. In the case of hemorrhage, blood should be permitted to egress from the needle spontaneously until the bleeding stops.
A series of CT images of the brain should be completed immediately following completion of the brain biopsy procedure in order to assess the possibility of intracranial hemorrhage. Animals should recover from anesthesia in sternal recumbency with the head elevated slightly above the level of the heart. Animals should be closely monitored for 12 hours post-biopsy before being discharged from the hospital.
Relative Merits of Alternative Brain Biopsy Procedures
Open (surgical) brain biopsy may be appropriate in certain clinical situations in which cortical architecture needs to be preserved, for leptomeningeal sampling, for superficially located lesions, and when a decompressive craniectomy with good cortical visualization may be helpful in addition to obtaining a biopsy sample.
Intraoperative Diagnosis Using the Smear Technique
The rapid cytological evaluation of a brain lesion from a biopsy sample can provide crucial information on operative management, medical management, chemotherapy, or radiation therapy. In people intra-operative cytological evaluation of smear preparations of brain tumors, supported by frozen and paraffin-embedded tissue, has become a routine procedure, and cytological profiles of smears of various types of human brain tumors have been well described. Smear preparations are generally wet fixed in 95% alcohol and stained with hematoxylin and eosin although toluidine blue, Giemsa, or Papanicolaou's stain may also be used.
In a recent study, tissue samples were obtained from lesions either by CT-guided stereotactic brain biopsy (44 samples) or intraoperatively during craniotomy (49 samples) and the results from the smear technique compared with those from sections of paraffin-embedded tissue. The overall diagnostic accuracy from samples obtained by both craniotomy and stereobiopsy was about 80%. This compares favorably with the 69–94% accuracy reported in some large series of human cases. The main advantages of this method of intraoperative diagnosis are speed, ease of preparation, technical simplicity, need for minimal equipment, high degree of cytological resolution compared to frozen preparations, low cost and small sample size required. A limitation of this system is that it is difficult to prepare adequate smear preparations in certain tough and coherent tumors (e.g., Schwannomas, fibrillary astrocytomas, and some meningiomas). Smear preparations provide excellent cytologic detail, however these differ from the conventional histologic appearance of HE-stained paraffin-embedded tissue. Experience is required in the correct interpretation of smear preparations.
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