1. eEdE
Authors: Poletto D1, Vale F2, Murtagh R1
Magnetic resonance guided laser-induced thermal ablation therapy: a visual review of key concepts
University of South Florida Morsani College of Medicine, Department of Radiology1; Department of Neurosurgery2

2. Disclosures
The authors have no conflicts of interest to disclose.

3. Purpose
The use of lasers for thermal ablation of brain lesions has recently become a viable option
largely due to the development of real-time, intra-operative thermal magnetic resonance imaging (MRI)
As MR guided laser thermal ablation therapy (MR-LiTT) becomes more widely practiced, the radiologist should become familiar with several key concepts of this therapy

4. Approach/Methods
Review procedure indications and pre-operative imaging needed for surgical planning
Discuss the procedure itself, focusing on intra-operative, real time imaging
Examine post-operative imaging findings and potential complications
Teaching points will be illustrated with images obtained using the Visualase Thermal Therapy System (Medtronic Neurosurgery, Louisville, CO) at a large tertiary care facility

5. Findings/Discussion

6. Laser Induced Thermal Therapy
980 nm diode laser and coaxial applicator system
laser supplies an optical fiber with a 1 cm long light diffusing tip
light distribution shape is cylindrical to ellipsoid
absorption of light photons by tissue causes coagulation necrosis
fiber surrounded by catheter 1.65mm in diameter
sterile saline infused through catheter for cooling
PIC DONE
Figure 1. Disposable coaxial laser applicator. (Medtronic Neurosurgery, Louisville, CO)

7. Laser Induced Thermal Therapy
Laser ablation controlled through computer workstation
houses 15 W laser generator
software integrates with standard MRI
displays thermal maps for real time, intra-operative monitoring
thermal maps can be used to create irreversible damage estimates
allows user to set temperature limits that cause deactivation of laser if exceeded
Figure 2. Workstation with computer interface and laser generator. (Medtronic Neurosurgery, Louisville, CO)

8. Procedure Indications
FDA approved to coagulate/necrotize soft tissue under MRI guidance in neurosurgery
Current uses include 1-5:
primary or metastatic tumors, usually smaller lesions
recurrence despite prior resection, chemotherapy, radiation
high risk surgical candidates
surgical inaccessibility of tumor
radiation necrosis
epileptogenic foci
Figure 3. MRI images from two different candidates for MR-LiTT (1.5 T Phillips Acheiva) Left: T1 post contrast of right frontoparietal glioblastoma multiforme Right: T2 of left mesial temporal lobe sclerosis.
Tumors:
Carpentier et al = metastatic brain tumors, average max. diameter 1.46 cm +/- 0.57
Jethwa et al = metastatic and primary, average max. diameter 2.4 cm +/- 0.85, average volume 7.0 cm3 +/- 9.0 cm3
Rao et al = recurrence v. radiation necrosis, average volume 3.66 cm3
Carpentier et al = recurrent GBM, average max volume 2.06 cm3 +/- 2.04
Our largest: GBM, measured 2.5 x 3.2 x 4.2 cm on pre-treatment MRI
Epilepsy:
Willie et al = patients with MTLE, w/ and w/o MTS, ablation of amygdala and hippocampus
Tovar-Spinosa et al = hypothalamic hamartoma
Curry et al = left cingulate tuber, amygdala, hippocampus, hypothalamic hamartoma, cortical dysplasia
TGH = MTLE, amygdala and hippocampus

9. Pre-procedural Imaging
stereotactic MRI brain with gadolinium
performed after stereotactic frame placement on patient
volumetric sequences allow for laser trajectory planning and determination of frame, arc settings
alternatively can perform stereotactic non-contrast computed tomography (CT) and fuse with prior MRI, or use optical navigation software
Video 1. Click for video of pre-operative, non-contrast CT (Philips Brilliance 16P, 120 kV, 138 mAs, slice thickness =1.00mm) showing components of the stereotactic frame placed prior to laser ablation on a patient with mesial temporal lobe sclerosis.
VIDEO DONE

10. Laser Applicator Placement
Stereotactic arc attached to frame
enables laser catheter placement at previously determined coordinates
optimal laser trajectory is along long axis of the lesion, dividing the lesion into equal parts
Stab incision, twist drill hole through skull, dura puncture
Laser applicator system inserted into brain and secured with custom bone anchor
Figure 4. Graphic depicting configuration of stereotactic arc and frame with guiding device. Cranial bone anchor is placed and laser introduced through the anchor. Frame/arc then removed (Medtronic Neurosurgery, Louisville, CO).

11. Final Pre-treatment Planning
Patient transferred to MRI suite, placed in scanner
3 dimensional T1 GRE sequence acquired
check applicator placement, choose plane(s) for ablation monitoring
plane should contain whole applicator and lesion
Test pulse applied (3-4W, <60 seconds) by laser
confirm adequate coverage of lesion by ablation zone
PIC DONE
Figure 5. Applicator placement into mesial temporal lobe confirmed with gradient echo T1 sequence. Applicator appears as a linear hypointense artifact caused by air within the outer catheter.

12. Thermal Ablation Outer catheter primed with saline
cools fiber and surrounding tissue to prevent tissue carbonization
Temperature limits set by user
placed near adjacent critical structures to prevent damage
1-3 points, < 50° C
Treatment dose: 10-15W, seconds per ablation
Number of ablations dependent on size of lesion
can retract optical fiber inside cooling catheter (mm)
Figure 6. Light diffusing tip of laser applicator system (Medtronic Neurosurgery, Louisville, CO).

13. Intra-operative Monitoring
Magnetic resonance thermal imaging (MRTI)
Dynamic thermal maps
color-coded fast spoiled gradient echo sequence (SPGR)
5 seconds per acquisition, run repeatedly for real-time monitoring
Thermal imaging achieved by shifts in proton resonance frequency 6
linear relationship to temperature due to temperature dependent alterations in hydrogen bonds of H20
PIC DONE
Temperature change causes hydrogen protons to shift to lower frequency at higher temperatures.
These resonant frequency shifts are measured by phase mapping, where you subtract phase distribution at a reference temperature from the phase distribution at the new temperature.
Figure 7. Color coded thermal map showing ablation of right amygdala and hippocampus in a patient with medial temporal lobe epilepsy (MTLE). Treatment included 3 ablations at 12W, for approximately 180 seconds each.

14. Intra-operative Monitoring
VIDEO DONE
Video 2. Click for video of intra-operative thermal imaging (SPGR, FOV = 220 mm, matrix 256 x 256, TE = 20 ms, TR = 20 ms, flip angle 20°) from the same patient. Video is without color overlay to show hypointense signal in ablation zone, caused by temperature dependent prolongation of T1 relaxation 7.

15. Intra-operative Monitoring
Irreversible damage estimates
Color-coded images created using an Arrhenius model of cell death
mathematical formula based on the time and temperature dependence of protein denaturation 2
calculated per voxel
Thermal maps and damage estimates superimposed on original T1 images for anatomic reference
Procedure concluded when irreversible damage estimate covers target area
PIC DONE
Figure 8. Irreversible damage estimate in the same patient, generated from dynamic thermal maps, showing total ablation zone in orange.

16. Immediate Post-procedure Imaging
T1 post gadolinium (Gd) sequence
Performed prior to removal of laser applicator
confirm adequate size of total ablation zone
zone contained within an enhancing rim
represents irreversibly damaged tissue with a rim of deoxyhemoglobin 7-8
Followed by return to operating room for applicator removal or additional laser ablations
PIC DONE
Figure 9. Immediate post-procedure T1+ Gd (1.5 T Philips Achieva) sequence showing enhancing rim of ablation zone surrounding the laser applicator.

17. Post-operative Care Patients admitted for overnight observation
Discharge often possible the following day
Post-operative steroid taper and seizure prophylaxis
Potential complications:
damage to adjacent structures
hemorrhage
worsening edema
short term memory loss
seizure
Curry et al  3.8 days average
Jethwa et al  most the next day
Carpentier et al 2008  14 hours
Carpentier et al 2012  most the next day
Willie et al  1.6 days average
TGH  most the next day

18. Post-operative Imaging
Day 1 post-operative
T1 shows central hyperintensity with hypointense rim; represents methemoglobin produced by coagulation necrosis surrounded by peripheral edema 7-8
corresponding reversal of this pattern on T2, FLAIR
axonal swelling at periphery of ablation may account for rim of restricted diffusion 7
Figure 10. Click to view a day 1 post-operative MRI after ablation for MTLE showing the changes listed above (1.5T Philips Achieva; T1, T2, FLAIR, DWI, ADC).

19. Post-operative Imaging
Day 90 post-operative
T1 shows decreased central hyperintensity; T1 + Gd shows decreasing peripheral enhancement
decreasing edema on T2, FLAIR sequences
resolution of restricted diffusion
changes begin within one month of ablation, continue over 4-6 months 8-9
Figure 11. Click to view a 3 month post-operative MRI in a different patient, also after ablation for MTLE, showing the changes described above (3T GE HDX; T1, T1+ Gd, T2, FLAIR, DWI, ADC).

20. Post-operative Imaging
Volume estimates
track changes in ablation zone size by measuring volume of peripherally enhancing lesion on T1+ Gd
rapid increase in ablation zone volume over 24 hour period, often reaching >200% 4, 10
slower growth can then occur for a period of 1-2 weeks
followed by decrease in volume to near pre-treatment size by 1-6 months 2, 4
Figure 12. Click to view coronal T1+ Gd MRI obtained at 24 hrs post, and 6 m post ablation for MTLE, showing decreasing size of enhancing rim (3T GE HDX).

21. Post-operative Imaging
Assessing for recurrence
local recurrence of tumor within the ablation zone
volumetric changes on T1+Gd
greatest lesion growth usually within 24 hrs; suggests 24 hr post scan, rather than immediate post, is best baseline 10
expect slower growth for additional 2 weeks 4
Signal intensity differences 9
changes in signal intensity on T1, T2, GRE, and FLAIR from pre- to post- scans, for multiple time points
signal intensity changes were different between success versus recurrence at all time points on T1 and T2 GRE sequences
Figure 13. Click to view a 1 year post operative MRI following mesial temporal lobe ablation, showing encephalomalacia, and no appreciable contrast enhancement (3T GE HDX; T1, T1+Gd, T2, FLAIR, DWI, ADC)

22. Summary/Conclusion Time Important MR Sequences Imaging Findings
Pre-operative
Stereotactic MR including T1+Gd with volumetric sequences
Adequate lesion localization to plan laser trajectory
Intra-operative
3D T1 GRE, volumetric
Fast, color-coded, spoiled GRE
Irreversible damage map
Determine imaging plane for ablation
Dynamic thermal monitoring
Estimate of total ablation zone
Post-operative
T1+Gd at multiple time points
Other sequences (T2, FLAIR, T2 GRE, DWI, ADC) at multiple time points
Track changes in volume of total ablation zone
Track changes in signal intensity

23. Summary/Conclusion
Initial studies of MR guided laser thermal ablation have generated promising results, and the therapy is likely to become more widely practiced
Being familiar with the surgical technique, intra-operative MR sequences, and post-operative imaging appearance will enable the radiologist to play a more active role in the application of this therapy and have a greater impact on patient care.

24. References
Jethwa PR, Barrese JC, Gowda A, Shetty A, Danish SF. Magnetic resonance thermometry-guided laser-induced thermal therapy for intracranial neoplasms: initial experience. Neurosurgery. 2012; 71(1 Suppl Operative):
2. Carpentier A, McNichols RJ, Stafford RJ et al. Real-time magnetic resonance guided laser thermal therapy for focal metastatic brain tumors. Neurosurgery. 2008; 63(1 Suppl 1): ONS21-28.
3. Curry DJ, Gowda A, McNichols RJ, Wilfong AA. MR-guided stereotactic laser ablation of epileptogenic foci in children. Epilepsy Behav. 2012; 24(4):
4. Rao MS, Hargreaves EL, Khan AJ, Haffty BG, Danish SF. Magnetic resonance guided laser ablation improves local control for postradiosurgery recurrence and/or radiation necrosis. Neurosurgery. 2014; 74(6):
5. Carpentier A, Chauvet D, Reina V et al. MR-guided laser-induced thermal therapy (LITT) for recurrent glioblastomas. Lasers in Surgery and Medicine. 2012; 44:
6. Ishihara Y, Calderon A, Watanabe H et al. A precise and fast temperature mapping using water proton chemical shift. Magn Reson Med. 1995; 34(6):
7. Schulze PC, Vitzthum HE, Goldammer A et al. Laser-induced thermotherapy of neoplastic lesions in the brain – underlying tissue alterations, MRI-monitoring and clinical applicability. Acta Neurochir. 2004; 146:
8. Schwabe B, Kahn T, Harth T, Ulrich F, Schwarzmaier HJ. Laser-induced thermal lesions in the human brain: short- and long-term appearance on MRI. J Comput Assist Tomogr. 1997; 21(5):
9. Tiwari P, Danish S, Madabhushi A. Identifying MRI markers associated with early response following laser ablation for neurological disorders: preliminary findings. PLOS One. 2014; 9(12): e
10. Patel NV, Jethwa PR, Barrese JC et al. Volumetric trends associated with MRI-guided laser-induced thermal therapy (LITT)for intracranial tumors. Lasers in Surgery and Medicine. 2013; 45:

25. Acknowledgements
The authors would like to thank Natalie St. Denis, Lisa Distenfield, and Anil Shetty of Medtronic Neurosurgery, as well as Brad Fernald of Synaptive Medical, for providing information and images regarding the Visualase Thermal Therapy System. We also thank Haydy Rojas for facilitating the IRB approval process.

26. Author Information Dana Poletto, MD Resident, Diagnostic Radiology
University of South Florida Morsani College of Medicine
2 Tampa General Circle, STC 7028
Tampa, FL 33606
Fernando Vale, MD
Division Chief and Vice Chairman, Department of Neurosurgery and Brain Repair
2 Tampa General Circle
Ryan Murtagh, MD, MBA
Associate Professor, Diagnostic Radiology