John Rossmeis1 and Annie Chen2 1 Virginia Tech, Blacksburg, VA, USA 2 Washington State University, Pullman, WA, USA Brain biopsy is a diagnostic surgical procedure that involves the removal of pieces of tissue from the brain which are then subjected to neuropathological, molecular, genetic, or microbiological analyses in order to establish a definitive etiologic diagnosis for the observed lesion [1]. Brain biopsy can be performed using open or closed techniques, and excisional or incisional biopsies performed during open craniotomy are currently the most frequently employed brain biopsy techniques in veterinary medicine [2]. In cases where open surgical approaches to a brain lesion may not be a possible or an optimal approach to case management, closed stereotactic brain biopsy (SBB) techniques are often a viable alternative method for sampling brain tissue [3–5]. This chapter will review closed SBB procedures, in which a stereotactic headframe – or in the case of frameless procedures, other types of fiducial markers – is affixed to the animal’s head prior to the performance of a diagnostic imaging scan such that the target lesion can be precisely localized and referenced to the external headframe or fiducials [3–7]. The neurosurgeon then performs the biopsy procedure using a minimally invasive approach to the skull and burr‐hole craniectomy technique. While computed tomography (CT) and magnetic resonance (MR) imaging techniques are sensitive for the characterization of brain lesions, both of these modalities have limited specificity with the imaging features of neoplastic, vascular, and inflammatory brain diseases demonstrating significant overlap [8, 9]. Since CT and MR imaging provide only a broad list of differential diagnoses for the observed lesions, brain biopsy allows for a definitive histologic diagnosis of the observed lesions which can subsequently guide specific and optimal treatment strategies. The most common diseases diagnosed by brain biopsy in veterinary medicine are tumors and immune‐mediated and infectious encephalitides, although theoretically any lesion that can be accurately targeted with imaging can be sampled [3–5, 9, 10]. A common clinical indication for brain biopsy is to establish a definitive diagnosis in a canine patient that presents with a focal intra‐axial lesion with MR imaging characteristics that are consistent with a granuloma, neuroepithelial neoplasm, or infarction [8, 9]. Brain biopsy can be used to identify brain pathologies that do not require surgical treatment via open craniotomy, or to establish diagnoses in patients who are poor surgical candidates. Closed brain biopsy is contraindicated in patients with underlying coagulopathies, and should be approached with caution in animals with clinical signs or MR imaging features consistent with increased intracranial pressure (ICP), animals with caudoventral lesions, or systemic medical disorders that result in increased anesthetic risk [3–5, 11]. SBBfb is the most commonly described type of closed‐brain biopsy procedure performed in animals with clinical signs of intracranial disease [3–7, 11]. SBBfb procedures require rigidly affixing the animal to an external reference system (i.e. headframe) and subsequently acquiring a set of diagnostic imaging data with the patient in the headframe such that the location of the target intracranial lesion can be transformed from the two‐dimensional imaging data into three‐dimensional stereotactic coordinates. Numerous types of stereotactic headframes (Figure 19.1) have been developed and modified for veterinary applications, and contemporary frames are constructed from non‐ferromagnetic materials, such as titanium, thermoplastics, or aluminum, such that they can be used safely in CT or MR imaging environments [3,12–14]. Additive manufacturing techniques are also being increasingly utilized in veterinary neurosurgery, and several SBBfb approaches using patient‐specific 3D printed brain biopsy guides have been recently described [12–14] (Figure 19.1). Figure 19.1 Instrumentation used for frame‐based stereotactic brain biopsy. Dynatech with attached micromanipulator arm (a), Virginia tech custom (b), and Kopf 1530 M (c) MRI compatible stereotactic headframes. A dog instrumented in the Dynatech headframe is illustrated in the inset of panel (a). (d) Schematic of design components of commonly used brain biopsy instruments. Computer rendering of a 3D printed, skull contoured patient‐specific brain biopsy guide (e), and 3D reconstructed CT scan (f) demonstrating the surgically implanted biopsy guide in situ. Prior to SBBfb, animals should have a complete blood count, serum biochemic profile, urinalysis, coagulation profile (i.e. PT/aPTT), and indirect blood pressure performed to screen for the animal’s underlying risk factors for anesthetic or post‐biopsy complications [3, 11]. Ideally, the initial diagnostic MR imaging that identified the lesion that is intended to be biopsied should have been performed within two weeks of the planned SBBfb procedure to avoid registration errors that can be associated with lesion evolution or resolution [3, 4]. The target lesion is typically identified on an MR imaging scan of the animal’s brain that was performed for diagnostic purposes. Following induction of general anesthesia and clipping of the head as required for the desired surgical approach, the animal is placed in sternal recumbency upon a rigid backboard. The neurosurgeon then affixes the head of the animal to the headframe. The majority of external stereotactic headframes described in veterinary medicine utilize a three‐point immobilization system, which involve a patient‐specific bite block and ear bars [3] (Figure 19.1). A dental impression of the patient’s maxillary arcade is created using vinylpolysiloxane dental putty and molded into the bite block of the headframe. The patient is then placed into the bite block of the headframe, and the ear bars of the headframe placed into the horizontal ear canals. Memory foam or cloth pads can also be placed beneath the mandible to further support the head. Rigid patient immobilization can be further achieved by bolting the headframe baseplate to the rigid backboard using threaded nylon nuts and bolts placed through predrilled holes in the backboard or plastic C‐clamps [3]. Once the patient is immobilized, they are transported to the radiology suite for acquisition of diagnostic images while instrumented in the headframe. If an MR imaging‐compatible headframe is being used, CT or MR images can be used for stereotactic imaging [3, 6, 12]. Care should be exercised when transferring the patient onto and off the CT or MR imaging gantry, as this is a common potential source of patient movement and subsequent frame registration error. Regardless of the imaging modality used, the field of view (FOV) must include the headframe apparatus, and this can significantly limit the types of coils that can be used for MR imaging. The accuracy of the target coordinates on the imaging will be correlated to the resolution of the imaging matrix. The precision of the Z coordinate is directly related to the slice thickness, and the magnitude of error for the X and Y coordinates will be related to the pixel size [1]. When performing stereotactic MR imaging, the authors minimally acquire T2W sequences in three planes and pre‐ and post‐contrast 3DT1W (isotropic <1 mm slice thickness with no gap). If using CT stereotactic imaging, pre‐ and post‐contrast images should also be obtained using <1 mm slice thickness, with no gap [1, 3]. DICOM formatted images of the diagnostic MR and stereotactic imaging dataset(s) are imported into an image analysis software package, and the diagnostic and stereotactic images are co‐registered using the automated mutual information co‐registration software feature. The neurosurgeon then uses the multiplanar reformatted image software interface to determine and visualize the desired stereotactic coordinates and trajectories for lesion biopsy [1, 3] (Figure 19.2). When planning the target location, it is optimal to choose a target location that is associated with both clinical and diagnostic imaging; evidence of pathology, areas of hemorrhage, and necrosis should be avoided, and the contrast‐enhancing lesion burden should be sampled whenever possible [3–5, 15]. In general, the biopsy needle entry point and trajectory are planned to traverse the shortest distance of normal brain between the skull and the target, and simultaneously avoid sulci, major vasculature, and ventricular structures. However, depending on the lesion location, geometry, and position relative to critical structures, the shortest path to the target is not always optimal. Rostrocaudal (Z) coordinates are measured from the internal linear (ear bar) reference markers (Figure 19.2). Mediolateral (X) and dorsoventral (Y) coordinates and/or angular trajectories are measured directly from DICOM images using osseous anatomic landmarks, including the external sagittal crest and external surface of the skull, referenced to the rostrocaudal bars of the headframe. The target depth is measured from the external surface of the intended craniectomy defect to the intended distal most position of the biopsy needle within the lesion. The final stereotactic (X, Y, and Z) coordinates are verified and stored in the planning software and registered to the headframe [1, 3]. Figure 19.2 Frame‐based stereotactic brain biopsy planning procedure with simulated biopsy needle placement (a, arrow). CT images are obtained with the patient instrumented in the headframe (a–e), and the diagnostic MRI images co‐registered and fused with the stereotactic CT dataset (inset, a). The neurosurgeon imports stereotactic images into multiplanar reformatting software, plans the biopsy trajectory and target depth (intersection of colored crosshairs in b–d), and determines the X, Y, and Z stereotactic coordinates. Panels e and f illustrate the headframe and patient references from which the stereotactic coordinates are measured. The neurosurgeon then chooses the type of instrument that will be used to harvest the biopsy. Multiple biopsy instruments are available for SBB, but they operate using three basic principles: side‐cutting needles, suction coring devices, or microforceps (Figure 19.1). Side‐cutting needles, such as the Nashold, Sedan, Latinen, and Backlund spiral, are the most frequently described instruments used in veterinary SBB applications [3–5,10–14]. These needles produce a sample size of 2×8–10 mm. When microforceps are used they are introduced through a biopsy cannula and typically retrieve a biopsy sample in the 1–2 mm3 range. Advantages of side‐cutting needles compared to microforceps include larger sample size and superior preservation of cellular cytoarchitecture. In humans, side‐cutting needles are associated with a higher incidence of symptomatic hemorrhage, which may be related to their sample size or the tissue tearing that occurs as the needle is turned within the brain [16]. The Shores–Little biopsy device (Figure 19.1) is an example of a suction coring instrument that is manufactured specifically for veterinary brain biopsy applications, although it was designed for use in open, ultrasound‐guided biopsy procedures. A disadvantage of the Shores–Little biopsy device is its relatively short working length, which can limit its utility for use in closed SBB applications. Head‐to‐head comparisons of the diagnostic yield, tissue quality, and adverse effect profiles resulting from the use of different biopsy instruments have yet to be performed in veterinary patients with intracranial disease. After the biopsy is planned, the neurosurgeon can elect to perform a phantom simulation to further verify the plan [17]. The phantom simulation involves attaching the micromanipulator arm to the stereotactic headframe and simulating the biopsy using a needle blank that is seated in position at the desired needle entry point into the calvarium [3, 17] (Figure 19.2). A CT or MR imaging scan is then repeated to include the headframe and attached needle phantom using the identical image acquisition parameters as the initial stereotactic scan for each patient. Following stereotactic planning, SBBfb can be performed in the operating room without image guidance, or with image guidance in the CT suite [3–5, 15] (Figure 19.3
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Brain Biopsy Techniques
Introduction
Indications and Contraindications
Frame‐based Stereotactic Brain Biopsy (SBBfb)
SBBfb Technique
Preoperative Evaluation
Headframe Placement and Acquisition of Stereotactic Images
SBBfb Planning
SBBfb Procedure
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