Preclinical Study of MRgFUS Ablation of the Lumbar Medial Branch Nerve: Functional Outcomes and Histology
Elena Kaye1, Sebastien Monette2, Majid Maybody3, Stephen B Solomon3, and Amitabh Gulati4

1Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 2Comparative Pathology, Sloan Kettering Institute, New York, NY, United States, 3Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 4Anesthesiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States

Synopsis

The main goals of this preclinical study were to determine whether direct MRgFUS ablation of the lumbar MB nerve leads to functional changes and to study the extent of the thermal damage to the targeted and adjacent tissues, including neurologic structures. We found that direct FUS ablation of the lumbar MBN achieves thermal necrosis of the targeted nerve with minimal thermal damage of the adjacent bone and muscle tissue. The extent of the cellular changes in bone is limited to a few millimeters with no changes in the spinal cord, confirming the protective effects of spine bone rapidly attenuating the ultrasound. No functional changes were observed.

Introduction

Up to 40% of Chronic Low Back Pain cases involve facet joints 1 which may be denervated by subcutaneous lumbar medial branch nerve (MBN) radiofrequency ablation. In a recent clinical study of MRI-guided Focused Ultrasound (MRgFUS) ablation of the facet joint 2, no improvement in pain scores was reported by 40% of the patients, potentially due to incomplete destruction of all small nerves innervating the joint. Technical feasibility for using MRgFUS to target the MBN before it branches into small nerves of the facet joint was recently demonstrated in an acute swine model 3. While feasible, currently, direct FUS ablation of spine is not clinically practiced due to potential risk of damaging spinal cord and lumbar nerve roots. The main goals of this project were to determine whether direct MRgFUS ablation of the lumbar MB nerve leads to functional changes and to study the extent of the thermal damage to the targeted and adjacent tissues, including neurological structures.

Methods

Three Yorkshire swine underwent unilateral ablation of the MB nerves using ExAblate 2000 FUS system and a GE 3 T MRI scanner after institutional animal care and use committee protocol approval. The intubated animals were positioned into a tilted-supine position to provide access to the space between the transverse (TP) and articular processes (AP)(Fig 1a). Two to four nerves were ablated in each animal using 3 - 9 sonications per nerve. Ultrasound frequency was 1.35 MHz and acoustic energy was 500 - 710 J. Thermal dose was calculated by the treatment planning software. Contrast-enhanced (CE) imaging was performed immediately after the treatment using MRI and 48-hours post-treatment - using computerized tomography (CT). The animals were maintained on preventative pain medications for 48 hours following the treatment. Assessment of pain, behavior, ambulation and gait was performed twice a day. After euthanasia, lumbar spine was fixed in formalin and decalcified. Decalcified sample was sectioned transversely into 5 mm thick slices, analyzed for gross pathology and processed routinely for histology, using hematoxylin and eosin (H&E) staining.

Results

All targeted nerves received lethal thermal dose (Fig 1b) in a location corresponding to non-perfused region visible between the transverse and articular processes on CE-MRI (Fig 1c,d) and CE-CT images (Fig 2), with tissue near the nerve root, superior to the ablation, appearing normal (Fig 2). No changes in bone contrast uptake were visible on CT. On CE-MRI bone surface near ablation appeared slightly more hypo-intense than bone of the untreated side (Fig 1c, arrowhead). No changes in animal behavior and functions were observed and no signs of superficial or deep pain were detected. There was no difference in animals’ ambulation, gait or pain between the treated and untreated sides. On gross pathology (Fig 2), the targeted region exhibited changes consistent with thermal damage and hemorrhage was observed as brown rim surrounding the ablation region in muscle and penetrating 2-5 mm into the bone. The gross appearance of the nerve root slices was normal. Histological analysis confirmed that changes in bone tissue did not extend deep towards the spinal canal leaving 5 to 7 mm of intact bone between the ablation and the spinal canal (Fig 3). Compared to a normal nerve (Fig 4a), treated nerve exhibited stromal hyalinization and nuclear pyknosis (Fig 4b) consistent with coagulative necrosis. The vessels near the ablated nerve appeared necrotic with signs of thrombosis. Muscle adjacent to the nerve was necrotic, with macrophages infiltrating the periphery of the ablation zone (inflammatory reaction). Compared to normal bone tissue (Fig 4c), the bone adjacent to the MBN exhibited coagulative necrosis: shrinkage, cytoplasmic hypereosinophilia and nuclear pyknosis of osteoblasts and hematopoietic cells, necrotic vessels, and hemorrhage. Spinal cord showed no histological changes. The nerve root sampled immediately above the ablation site (Fig 5) appeared normal.

Discussion

Direct FUS targeting of the lumbar MBN achieves thermal necrosis of the nerve with minimal necrosis of the adjacent bone and muscle tissue. Visualization of spine bone necrosis is challenging on MRI due to short relaxation time of the cortical bone. The extent of bone necrosis is limited to the superficial layer of the bone, with no changes in the spinal cord, confirming the protective effect of spine bone acoustic attenuation 4. No changes in the nerve roots demonstrate that small size of the individual FUS lesions makes FUS ideally-suited for neurological applications requiring minimal ablation “foot-print” to spare adjacent critical structures.

Conclusion

The functional and histological outcomes of this study provide preliminary evidence of the safety of direct MRgFUS ablation of the MBN, potentially broadening the bone MRgFUS applications to spine malignancies.

Acknowledgements

We thank Jacob Chen for technical support with MRgFUS system and Dr. Govindarajan Srimathveeravalli for support with CT imaging session.

References

1. L. Manchikanti, V. Singh, V. Pampati et al., Evaluation of the relative contributions of various structures in chronic low back pain. Pain Physician 4 (4), 308-316 (2001).

2. E. Weeks, M. Platt and W. Gedroyc, MRI-guided focused ultrasound (MRgFUS) to treat facet joint osteoarthritis low back pain—case series of an innovative new technique. Eur Radiol 22 (12), 2822-2835 (2012).

3. E. Kaye, A. Gulati, S. Monette et al., Evaluating MRgHIFU Ablation of the Lumbar Medial Branch Nerve in an Acute Swine Model. 15th International Symposium on Therapeutic Ultrasound, Utrecht, 2015.

4. S. J. Scott, V. Salgaonkar, P. Prakash, E. C. Burdette and C. J. Diederich, Interstitial ultrasound ablation of vertebral and paraspinal tumours: parametric and patient-specific simulations. International Journal of Hyperthermia 30 (4), 228-244 (2014).

Figures

Figure 1. Example of MRgFUS ablation: (a)-position of the animal, FUS beam and focal spot, (b)-corresponding thermal dose (in blue), and lack of perfusion (arrowhead) on CE-MRI (c). Ablated bone appears slightly more hypointense than the bone on the un-treated side similar to treated side.

Figure 2. a. On CE-CT, ablation is visible in muscle as non-perfused region (arrowhead). On gross pathology, ablation of muscle (arrowhead) and brown rim of hemorrhage are seen in muscle and bone (arrow). The nerve root, superior to this ablation, appeared normal on imaging (b) and pathology (d).

Figure 3. Low magnification histology of the targeted region with the MBN (arrow) appearing between the TP and AP. Muscle tissue lateral to the nerve is ablated, and dark red rim in the bone (dashed line) shows propagation of thermal damage (*) in the bone. Scale bar 1 mm.

Figure 4. High magnification histology images of normal and ablated MBN and adjacent bone. a-b: stroma around the MBN (black arrow) and appearance of nuclei (white arrow) change in ablated nerve. In bone, arrows point at the normal (c) and necrotic (d) osteoblasts. Hemorrhage is indicated with *. Scale bar 50 um.

Figure 5. Low magnification histology of the slice (Fig 2d) containing the nerve root exiting through the foramen. High magnification image of the nerve root (box) shows normal root ganglion (*).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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