Focused Ultrasound (HIFU) Lab

• The goal of this study was to investigate near-field heating in patients treated with the InSightec fibroid system. 
• Accurate measurement of near-field heating in adipose tissue:
  • shorter treatments
  • preventing injury in healthy tissues

 
Temperature change from the baseline in the same patient. Intersections of the beam axes and the slice are shown as circles, location of the measurement as “cross”

Publications:

Ozhinsky E, Kohi MP, Ghanouni P, Rieke V: T2-based temperature monitoring in abdominal fat during MR-guided focused ultrasound treatment of patients with uterine fibroids. J Ther Ultrasound 2015, 3:15.

• Benign but locally aggressive soft tissue tumors that arise from fibroblast cells
• Conventional therapies: resection, radiation, chemo
  • Recurrence rate up to 50%
• Rare disease (2-4 per million people/year), but they all seem to end up at UCSF
• Patient population: pediatric, young adult
• Can MRgFUS be an alternative treatment?
  • Can T2 mapping during treatment predict NPV?

 
Desmoid tumor before MRgFUS treatmen.

Comparison between T2 maps (a) and post-contrast images (b) for the same location for patient 2  The non-perfused volume (NPV) appears dark on the post-contrast images. Arrows show gaps in the NPV, which correspond to areas with low T2 in the T2 maps. 

Abstracts:

Ozhinsky E, Bucknor M, Rieke V. T2-Mapping as a Predictor for Non-Perfused Volume in MRgFUS Treatments of Desmoid Tumors
The 16th International Symposium on Therapeutic Ultrasound, Tel Aviv, Israel, March 2016
ISMRM 24rd Annual Meeting in Singapore, May 2016

• Proton resonant frequency shift (PRF) thermometry:
  • commonly used for temperature monitoring in water-based tissues 
  • fails to detect temperature change in tissues with high lipid content, such as bone marrow.
• Current clinical protocols rely on measurement of temperature change of adjacent muscle
• Poor accuracy of temperature measurement, sub-optimal ablation

Could T2-based thermometry be used to monitor the temperature in bone marrow during focused ultrasound ablation?

T2 measurement in ex vivo bone marrow during and after the heating. (a) Localizer image showing the ultrasound transducer in the table. (b) T2 map during heating, showing the ROI. (c) Plot of T2 values within the ROI over time.

• We measured a T2 elevation of 269 ms. 
• Assuming the T2/temp coefficient of 7 ms/°C, this corresponds to a temperature rise of 38°. 
• The ex-vivo experiment shows that it takes 10-15 minutes for the marrow to return to the baseline temperature. 

The in-vivo experiment showed excellent correspondence between the area of T2 elevation in marrow during the ablation and the resulting non-enhancing area in the post-contrast images:

T2 measurement in in vivo bone marrow: (a) T2 map during ablation of a single sonication, showing the ROI; (b) post-contrast 3D Fast SPGR image after ablation (total of six sonications per location); (c) plot of T2 values within the ROI over time; the highlighted area shows the approximate duration of the sonication.

• We have demonstrated the measurement of heating with T2-based thermometry in vivo in the marrow during bone ablation. 
• The ability to monitor the temperature within the bone marrow 
  • allowed visualization of the heat penetration into the bone.
  • important for local lesion control and treatment of osteoid osteomas.

Publications:

Ozhinsky E, Han M, Bucknor M, Krug R, Rieke V. T2-based temperature monitoring in bone marrow for MR-guided focused ultrasound. J Ther Ultrasound. 2016 Nov 17;4:26.

• FUS is a noninvasive method for treating bone tumors and palliating pain. 
• To ensure proper heat deposition, temperature mapping is necessary. 
• Proton resonant frequency shift MR thermometry is not appropriate for cortical bone (T2 ≈ 0.5 ms).
• Monitoring thermal dose has been only possible by using temperatures in surrounding tissues. 

• T1 and T2 change with temperature, resulting in MR signal change (Parker 1984, Ghandi 1998).
• Ultrashort echo-time (UTE) imaging can generate signal from cortical bone. 
• UTE depicts bone signal change in a region of temperature increase  (Miller 2012, Ramsey 2015).
• Our goal: Demonstrate UTE imaging to quantify T1 changes in cortical bone for temperature mapping and accelerate acquisition.

Reconstructed Image and T1 Maps

Publications and Abstracts:

• Han M, Scott SJ, Ozhinsky E, Salgaonkar V, Jones PD, Diederich CJ, Rieke V, Krug R. Quantifying Temperature-Dependent T1 Changes in Cortical Bone Using Ultra-Short Echo-Time MRI. Magn Reson Med. Magn Reson Med 2015, 74:1548-1555.
• Han M, Jiang W, Krug R, Larson P, Rieke V. Acceleration of 3D UTE Imaging to Quantify Temperature-Dependent T1 Changes in Cortical Bone. ISMRM 24rd Annual Meeting in Singapore, May 201

• Mild hyperthermia (HT, 40 – 44 °C) augments radiation, chemotherapy, drug delivery

  • Targeted drug delivery – liposomes
  • Anti-tumor immunity stimulation
  • Immune modulation for cancer vaccines
  • Hormone therapy

• Feasibility of prostate hyperthermia with endorectal ultrasound applicators has been demonstrated in clinical trials

Sonication Patterns

Hyperthermia Control

• Real-time MR Thermometry
• Continuous steering of the ultrasound beam towards the coolest spot within the region of treatment

 
Control flow diagram of the MR Thermometry-based hyperthermia delivery system. Real-time MR Thermometry imaging controls the focus and power output of the ultrasound beam, ensuring constant and uniform heating within the region of treatment.

  
User interface of the MR thermometry-guided hyperthermia application, showing a temperature map overlaid on top of the coronal magnitude image (top-left), sagittal and axial navigator images with the phantom in a water bucket on top of the focused ultrasound transducer (top-right, bottom-left), and control panel with region of treatment shape selector (bottom-right).​

Examples of prescribed regions of treatment, and corresponding MR thermometry images, acquired during the heating.​

 

Plot of the temperature values within cells of the ROT (multiple colors) and mean temperature of the whole ROT (black) for the square heating pattern.

• We have implemented a real-time MR thermometry-guided system for hyperthermia delivery within constrained regions with the ExAblate prostate array and validated it in phantom experiments.
• Future work includes implementation of faster accelerated imaging, investigation of heating complex 3D regions, and in-vivo validation.

Abstracts:

• Ozhinsky E, Salgaonkar VA, Diederich CJ Rieke V. MR Thermometry-guided Prostate Hyperthermia with Real-time Ultrasound Beamforming and Power Control
  The 16th International Symposium on Therapeutic Ultrasound, Tel Aviv, Israel, March 2016
  ISMRM 24rd Annual Meeting in Singapore, May 2016
• Ozhinsky E, Salgaonkar VA, Diederich CJ Rieke V. MR Thermometry-guided Ultrasound Hyperthermia of User-Defined Regions Using the ExAblate Prostate Ablation Array. ISMRM 25th Annual Meeting in Honolulu, HI, April 2017

Sonication strategies

• This project proposed and evaluated electronic beam steering, multi-focal patterns, and sector vortex beamforming approaches in conjunction with partial array activation.
• Turning off a percentage of the outer array to increase the f-number increased the focal size with a decrease in focal gain.
  
  Graphical abstract of sonication strategies for volumetric ultrasound hyperthermia.
• Temperature distributions with MR thermometry for a sonication cell rapidly sweeping a single focal zone across four spot positions
• Sonications with the vortex mode number 4 provided the focused pressure fields around the axis of the beam and the heated volume was enlarged, for higher mode numbers and for lower number of active elements.
  
  Heat distributions for sonications using the electronic beam steering and vortex beam mode with partial array elements.
• Volumetric HT distributions in the phantom after prolonged heating with a slow temperature rise.
• Sonications were respectively performed with the mode number 4 and 80% and 100% active elements.
• The volumes of 18.8 cm³and 29.7 cm³were estimated by the 4^oC contour areas with 100% and 80% active elements, respectively.
• Heating with 80% active elements produced 1.58 times larger volume than that of 100% active elements.
  
  Volumetric HT distributions in the phantom comparing 100% and 80% array activation. (a) Temperature maps at 600 secs are shown and (b) time-dependent profiles of temperature measured in an ROI at the focus is plotted. A black solid line in the MR temperature map indicates an area for a temperature rise above 4 ^oC.

Acoustic and thermal simulation

• We developed an acoustic and thermal simulation framework to calculate the 3D acoustic intensity and temperature distribution resulting from the proposed beamforming and scanning strategies.
  
  Top view (top row), acoustic intensity (middle row), and corresponding steady-state hyperthermia temperature distributions (bottom row) targeted at Z = 160 mm.
• This project demonstrated the feasibility of large volume hyperthermia beam patterns using the ExAblate body system.
• The proposed methods were applicable to all other systems comprising of a concentric-ring sectored-vortex phased array.
• This technique could be used in the future with the mechanical movements for large volume HT treatments using the ExAblate 2000 body system.

Abstracts:

• K. Kim, M. Adams, C.J. Diederich, E. Ozhinsky, Sonication strategies for delivery of volumetric ultrasound hyperthermia using the ExAblate body array, 7^thInternational Symposium on Focused Ultrasound Symposium (Poster presentation, Young Investigator award)
• K. Kim, M. Adams, C.J. Diederich, E. Ozhinsky, Sonication strategies for delivery of volumetric ultrasound hyperthermia using the ExAblate body array, Society for Thermal Medicine Young Investigator Symposium (oral presentation)