Stereotactic biopsy for brain lesions: Doing more with less

INTRODUCTION

Based on the spatial coordinates detected in radiology, stereotactic biopsy (STB) is a tissue biopsy of any intracranial lesion through a small burr hole. This mode of attaining tissue biopsy is employed when the lesion is not ideal for open surgical resection, possibly due to its smaller size, depth, multifocality, or diffuse nature. Stereotactic biopsy is used in clinical conditions with lesions situated in the eloquent cortex or when a pathological diagnosis is mandatory for further management.^[1] Stereotactic biopsy was first conceived by Clarke and Horsley, who, in the early 1900s developed the primary device for targeting cerebellar structures in animals.^[2,3] Since its invention, the technique has imbibed and adapted its fundamentals using the latest advances. At present, it is the least invasive procedure to obtain a sample for pathological diagnosis and evaluation for therapeutics in patients with intracranial lesions. The procedure can be carried out with a frameless or a frame-based stereotactic method, neuro navigation, or robotic assistance in surgery. Recent studies have failed to find statistically significant differences between frameless and the frame-based biopsy methods in the diagnostic yield, mortality, morbid complications, and after-procedure complications.^[4] Commonly employed frame-based systems are the Cosman Roberts Wells (CRW) (Integra et al. Cincinnati, USA) and Leksell® (Elekta et al.) stereotactic systems. Frameless or stereotactic navigation systems employ several small fiducial markers fixed over areas of the scalp, which act as reference landmarks.

Despite the wide utilization of stereotactic biopsy, the results found in various studies on STB are controversial and non-comparable.^[5] Our department has performed frame-based brain biopsies since 2018. Here, we share our experiences of stereotactic biopsy performed with the frame-based system under local anesthesia over the past 5 years. Besides focusing on the clinical spectrum and diagnostic yield, the study also highlights the essential anesthetic and surgical techniques stepwise to fine-tune the routine practice in clinics of stereotactic biopsy.

MATERIALS AND METHODS

All the patients who had undergone a frame-based stereotactic biopsy between January 2018 and December 2022 were eligible for inclusion. The data were retrieved from the hospital information system. The collected parameters were the age of the patient, sex, provisional/working diagnosis, and comorbidities. Pre-operative radiological diagnosis, the anatomic region involved in the lesion, and the Karnofsky’s performance status (KPS) score were noted. Since the procedures were performed under scalp block, the patient’s cooperation undergoing the frame-based STB was crucial. The number of samples taken from the lesion, duration of hospital stays, or any complications following the procedure was recorded. Intraoperative impression and histopathology provided a base for further line of treatment.

All procedures were performed using a CRW® stereotactic frame. Pre-operative magnetic resonance imaging (MRI) scans under neuro navigation protocol were performed at admission. After the frame was applied, a contrast-enhanced computerized axial tomography (CAT) scan was utilized to target the lesion and to calculate Cartesian coordinates. Using these measurements on three axes (X, Y, and Z), the targeted lesion was biopsied under an aseptic condition. Routine post-operative care was provided as per the departmental protocol. Post-procedure CAT scan was done to look for the biopsied target lesion.

Stereotactic frame

The CRW stereotactic-based frame is a universal compact head ring assembly. The significant parts of this assembly include a universal head ring, adapter plates, curved and short head posts, crossbars for pediatric patients, pointers, tubes, localizer frames, screws, pins, and head ring wrenches. [Figure 1a-d] The attachments of the CRW frame are fixed on the patient’s head and are carried out by drawing a canthomeatal line, and the frame is kept parallel to it, which acts as a reference line. This canthomeatal line corresponds to the radiological line drawn from anterior to posterior commissure in the midline.

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Figure 1:

(a) Cosman-Roberts-Wells stereotactic biopsy set, (b) inserting biopsy needle, (c) pins placed in orbitomeatal line, (d) planning in work station.

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Scalp block

Scalp block is the selective blockade of specific scalp nerves using local anesthesia. The benefits of scalp block can be utilized for different sub-types of awake cranial clinical procedures such as stereotactic-based biopsy, surgery for deep brain stimulation, and stereotactic radiosurgery. Relevant history and physical examination including airway examination and evaluation regarding suitability for awake procedure in terms of cooperation were performed.^[6]

The nerves that are blocked for scalp block were chosen according to the incision and craniotomy planned. For a complete scalp anesthesia, six nerves are blocked on both sides using about 40 mL of local anesthetic [Figure 2a-d]. Long-acting local anesthetic are administered along with epinephrine in concentration 1:200,000 to prolong the duration of action and reduce systemic absorption. Bupivacaine 0.5% is the most used local anesthetic agent. The maximum dose limit of local anesthetic is calculated according to body weight [Table 1, upper half].

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Figure 2:

(a and b) Showing front and side views, respectively, of cranial nerves to be blocked. A-Supratrochlear nerve, B-Supraorbital nerve, C-Zygomaticotemporal nerve, D-Auriculotemporal nerve, E-Lesser occipital nerve, F-Greater occipital nerve, G-Great auricular nerve. (c and d) Showing scalp and forehead sensory innervation with dermatome-wise distribution. V1: Ophthalmic nerve, V2: Maxillary nerve, V3: Mandibular nerve.

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Table 1: Maximum dose limit of local anesthetic according to body weight (upper half) and nerves to be blocked for craniotomy and their origin (lower half).

Local anesthetic	Maximum safe dose	Onset of action	Duration of action
Lidocaine 2%	4 mg/kg	60–90 s	20–30 min
Lidocaine with epinephrine	7 mg/kg	60–90 s	Up to 2 h
Bupivacaine 0.5%	2 mg/kg	10–20 min	4–6 h
Bupivacaine with epinephrine 0.5%	3 mg/kg	10–20 min	Up to 8 h
Nerve to be blocked	Origin	Anterior craniotomy	Posterior craniotomy
Supratrochlear	Ophthalmic branch of trigeminal V1	Blocked	Not blocked
Supraorbital	Ophthalmic branch of trigeminal V1	Blocked	Not blocked
Auriculotemporal	Mandibular branch of trigeminal V2	Blocked	Not blocked
Zygomaticotemporal	Maxillary branch of trigeminal V2	Blocked	Blocked
Greater occipital	C2 posterior ramus	Not blocked	Blocked
Lesser occipital	C2 and C3 ventral rami	Not blocked	Blocked

For sedation, before application of the block, initially a loading dose of 1 mg/kg dexmedetomidine is given intra venous in 20 min, followed by infusing continuously a maintenance dose of 0.1–0.7 mg/kg/h. Scalp block is given under aseptic conditions. 3–5 mL of local anesthetic is infiltrated using a 24-gauge needle for each branch which supplies sensory function of the forehead and scalp [Table 1, lower half].

RESULTS

DISCUSSION

Stereotactic needle biopsy is an established procedure for studying characters of lesions situated in the brain whose clinical picture is unclear or not found optimal for surgical management. The procedure can be done using frameless (navigation/robot-assisted) or frame based as in our study. Stereotactic needle biopsy is considered a prudent and precise approach for the management of deep-seated brain lesions and those located in eloquent areas.^[7]

Frame-based stereotactic biopsy employs a rigid frame fixed firmly over the patient’s head at the beginning of the procedure. This technique is based on three-dimensional coordinates, where the target point (intracranial lesion) is given a coordinate relative to a reference point. This reference point was defined over the frame based on the pre-operative imaging sources (intracranial CT and MRI). The major limitation of the frame-based biopsy technique is the complexity and maintenance of the frame. The patient’s discomfort and prolonged procedure time are additional disadvantages of this technique.^[8,9] The frameless neuronavigation system utilizes a pointer, a digitizer, and a fiducial system. The fiducials are placed on the patient’s scalp before imaging and are then used as a reference to allow for the target calibration relative to the patient’s head. Registering and transferring this spatial information allows a registered pointer and the biopsy probe to be projected onto the pre-operative images. By doing this, an accurate intraoperative navigation and targeting of the set lesion is achieved. The actual surgical duration is shortened since the imaging and planning of the target are separate from surgery concerning time and location. The major drawback of the frameless biopsy technique is because of more drift and tremor of the surgeon due to the complex hand-eye coordination as a pre-requisite for this modality.^[10,11]

The main reason to choose stereotactic biopsy rather than craniotomy is that stereotactic biopsies have minimal adverse effects with a high diagnostic accuracy rate. Stereotactic biopsy has advantages over open biopsy in tumors with characteristics like:

1. Lesions that do not result in mass effect or are not amenable to excision, such as deep-seated metastatic deposits or intrinsic brain tumors of doubtful nature;

2. Deeply located lesions or those found in eloquent regions or deep nuclei (e.g., basal ganglia and thalamus), for which open surgical procedure would result in unacceptably complications and

3. Infiltrative diseases (e.g., gliomatosis cerebri) that lack a clear brain-tumor interface and are less likely to be excised without significant loss of unaffected neural tissue.

Furthermore, if the lesion, on imaging or the disease progression, suggests an alternative pathology, such as an infectious or demyelinating disease, stereotactic biopsy is a well-considered first step rather than a more invasive procedure like craniotomy.

Tumors with high vascularity such as renal cell carcinoma, choriocarcinoma, or metastatic melanoma are relative contraindications. They are generally not approached with STB because of the high risk for hemorrhage, deranged coagulation parameters, bad general conditions, irritability, and noncompliance to cooperate during the procedure. In cases of metastatic tumors, if the patient’s condition is stable, primary underlying pathology should be looked for and treated it accordingly. Besides, tumors close to a major blood vessel, the vessel-rich Sylvian fissure, the cavernous sinus, should make the neurosurgeon consider the risk for hemorrhage. When possible, stereotactic biopsy should also be avoided in patients undergoing treatment with anticoagulant drugs.

The diagnostic correctness in our study of the frame-stereotactic biopsy technique was 95.0%. The accurate tissue yield in the frame-stereotactic technique was 84.21– 97.5%.^[12-15] In a study done by Jain et al. among 95 patients,^[12] accurate diagnosis was arrived at in 80 patients (84.21%), whereas Dorward et al. achieved a higher diagnostic yield of around 95% among 75 cases of frame-based biopsy.^[16] High-grade glioma was the most common tissue diagnosis, accounting for 40% of all cases. In the research conducted by Tsermoulas et al., in a total of 124 individuals, diagnostic accuracy was 93.5%, with Glioblastoma (GBM) being the most frequent finding (41.1%), followed by B-cell lymphoma (17.74%), which is similar to our study.^[14]

Historically, small biopsies yielded inadequate viable tissue for obtaining the essential molecular diagnosis; however, technological advancement resulted in even smaller specimen samples being analyzed by an array of molecular markers. Only with the availability of advanced pathological techniques and know-how, these biopsies are adequate to gain all necessary information for accurate impression in case open resection is not deemed necessary. As mentioned, 95% of our biopsies shed light on microscopic histology and molecular uniqueness of the tumor. A precondition for a correct molecular diagnosis is to acquire the sample out of the solid regions of the tumor. The neuropathologist must be well versed in working on small samples.

Surgical management of brain tumors is guided by three basic principles: Oncologic clearance, preserving and restoring function, and improvement in quality of life.^[17] Surgical decisions are based on achieving either one or more of these aims. GBM, WHO grade 4 is the most common malignant primary central nervous system tumor, with a poor prognosis of only 12–16 months survival despite adequate treatment consisting of maximal safe surgical resection, adjuvant or concomitant chemotherapy, and radiation therapy.^[18,19] Challenges in treatment are compounded by the significant heterogeneous nature of the tumor, microscopic invasion, and difficulty in differentiating margins of the lesion from normal brain intraoperatively.^[20,21] All glioma treatment depends on a tissue diagnosis, with molecular analysis supplementing histopathologic analysis. Where possible, gross total resection remains the gold standard. For lesions not amenable to gross total resection, a biopsy is recommended to achieve a convincing diagnosis if radiation and chemotherapy are considered adjuvant therapy to achieve progression-free survival.

The mean size of the tumors in our analysis was 2.43 cm, values that ranged from 1.8 to 3.75 cm. In a study by Dorward et al., the mean size of the lesion was 3.48 cm, with a range from 0.8 cm to 8 cm among the frame-based group.^[16] Various literatures suggests that the brain lesion volume influences the diagnostic yield. Larger lesions are associated with more accurate biopsies and vice versa. In the present study cohort, only one among the various biopsies was inconclusive. A previous study had an overall negative report in 15.79% of patients.^[12] Since a high index of suspicion was kept, the patient underwent a craniotomy and excision of the tumor, which was reported as a WHO Grade 4 GBM.

Neuro-oncology is changing rapidly; classification and treatment are based on indispensable immune-histochemistry and molecular biological data, highlighting the role of a biopsy in treating intracranial tumors.^[22] In 2012, Jakola et al. and Sanai and Berger documented that safe maximum tumor resection, made possible by the correct use of frameless image-guided surgery, is associated with better prolonged overall survival of both low-grade and high-grade gliomas.^[20,23] Meanwhile, the recently introduced WHO classification of brain tumors advocates for correct molecular profiling of tumors of the brain.^[24]

Although STB is a minimally disruptive procedure, severe complications can occur in up to 8% of cases. Thus, obtaining adequate quantities of diagnostic tissue with a minimum number of samples is of paramount concern.^[7] Bleeding is the most frequent operative complication encountered post-stereotactic biopsy, with symptomatic and asymptomatic hemorrhage incidence ranging from 1.3% to 59.8%. Kulkarni et al. divided new hemorrhages by lesion size and location and found that 41.1% of the 56 intraparenchymal hemorrhages were smaller than 5 mm in maximal length.^[25] Mizobuchi remarked that hemorrhages were lesser than 5 mm in size in 22 of the total 25 patients with post-biopsy hemorrhages.^[26] A high-density region < 5 mm at the site where the biopsy needle was inserted on post-operative CAT scans was not counted hemorrhagic; rather, it represents merely an postoperative change after stereotactic surgery.^[27]

Deeply located lesions associated with edema and dye uptake on contrast imaging, intraoperative rise in blood pressure in a non-hypertensive patient, and malignant glioma were autonomous risk factors associated with hemorrhage after stereotactic tissue acquisition.^[7,28-30] These results pointed toward the possibility of bleed occurring after biopsy increases in a higher grade of malignant tumors with abnormal vasculature. The mortality rate due to acquiring tissue stereotactically ranges from 0% to 4%,^[7] and total morbidity varies from 0 to 13%.^[30,31] Hence, careful optimization, correct acquisition of the desired lesion site, and intraoperative management has to be ensured while performing stereotactic needle procedures for higher-grade glial lesions, lymphomas, and lesions with high vascularity.

CONCLUSION

The stereotactic biopsy system should be considered an essential surgical tool in the neurosurgeon’s armamentarium and must be utilized in specific patient populations. The procedure is time-consuming but has a high diagnostic yield, aids in optimizing management, and improves patient care and outcomes.