MR-Cavitation Dynamics Encoded (MR-CaDE) imaging.
Authors: Gupta D, Kaovasia TP, Allen SP, Nielsen JF, Hall TL, Xu Z, Noll DC
To develop methods for dynamic cavitation monitoring of a non-invasive ultrasound mechanical ablation technology (histotripsy) in the brain and test its feasibility for treatment monitoring in ex-vivo brain in a human MRI scanner. A Gradient Echo (GRE) pulse sequence was modified with a bipolar gradient to perform MR-Cavitation Dynamics Encoded (MR-CaDE) imaging. Cavitation generated by histotripsy sonication was monitored using MR-CaDE imaging in ex-vivo bovine brain tissues on a <math xmlns="http://www.w3.org/1998/Math/MathML"> <semantics><mrow><mn>3</mn> <mi>T</mi></mrow> <annotation>$$ 3\mathrm{T} $$</annotation></semantics> </math> human MRI scanner. Bipolar gradients with a b-value of <math xmlns="http://www.w3.org/1998/Math/MathML"> <semantics><mrow><mtext>b</mtext> <mo>=</mo> <mn>50</mn> <mi>s</mi> <mo>/</mo> <msup><mrow><mtext>mm</mtext></mrow> <mrow><mn>2</mn></mrow> </msup> </mrow> <annotation>$$ \mathrm{b}=50\mathrm{s}/{\mathrm{mm}}^2 $$</annotation></semantics> </math> and smaller were used while a trigger was sent from the MR scanner to the histotripsy driving electronics. MR acquisition was performed with TE/TR: <math xmlns="http://www.w3.org/1998/Math/MathML"> <semantics><mrow><mn>19</mn> <mspace></mspace> <mtext>ms</mtext> <mo>/</mo> <mn>100</mn> <mspace></mspace> <mtext>ms</mtext></mrow> <annotation>$$ 19\kern.2em \mathrm{ms}/100\kern.2em \mathrm{ms} $$</annotation></semantics> </math> with 1.5-cycle histotripsy sonications at 1 pulse/TR. Feasibility of treatment monitoring was also evaluated for histotripsy through an excised human skull. The MR-CaDE imaging pulse sequence was used to perform treatment monitoring of cavitation generated by histotripsy with a temporal resolution of <math xmlns="http://www.w3.org/1998/Math/MathML"> <semantics><mrow><mn>0.5</mn> <mspace></mspace> <mtext>s</mtext></mrow> <annotation>$$ 0.5\kern.2em \mathrm{s} $$</annotation></semantics> </math> with a spiral readout. A decrease in the image magnitude and an increase in the phase was observed with an increasing number of histotripsy sonications. The magnitude image exhibited a peak loss of 50%, and the phase image exhibited a maximum increase of 0.64rad compared to the baseline signal level in the brain. The peak signal magnitude change aligned well with the array's geometrical focus, and the post-histotripsy lesion visualized on a DWI ( <math xmlns="http://www.w3.org/1998/Math/MathML"> <semantics><mrow><mtext>b</mtext> <mo>=</mo> <mn>1000</mn> <mspace></mspace> <mtext>s/mm</mtext> <msup><mrow><mo> </mo></mrow> <mrow><mn>2</mn></mrow> </msup> </mrow> <annotation>$$ \mathrm{b}=1000\kern.2em \mathrm{s}/{\mathrm{mm}}^2 $$</annotation></semantics> </math> ) scan with an alignment error of <math xmlns="http://www.w3.org/1998/Math/MathML"> <semantics><mrow><mn>0.71</mn> <mspace></mspace> <mtext>mm</mtext></mrow> <annotation>$$ 0.71\kern.2em \mathrm{mm} $$</annotation></semantics> </math> and <math xmlns="http://www.w3.org/1998/Math/MathML"> <semantics><mrow><mn>1.25</mn> <mspace></mspace> <mtext>mm</mtext></mrow> <annotation>$$ 1.25\kern.2em \mathrm{mm} $$</annotation></semantics> </math> in the transverse and longitudinal axes, respectively. The area of the histotripsy response using the spiral readout in the magnitude and phase images were <math xmlns="http://www.w3.org/1998/Math/MathML"> <semantics><mrow><mn>3</mn> <mo>.</mo> <mn>38</mn> <mspace></mspace> <mtext>mm</mtext> <mo>×</mo> <mn>5</mn> <mo>.</mo> <mn>62</mn> <mspace></mspace> <mtext>mm</mtext></mrow> <annotation>$$ 3.38\kern0.3em \mathrm{mm}\times 5.62\kern0.3em \mathrm{mm} $$</annotation></semantics> </math> and <math xmlns="http://www.w3.org/1998/Math/MathML"> <semantics><mrow><mn>10</mn> <mo>.</mo> <mn>92</mn> <mspace></mspace> <mtext>mm</mtext> <mo>×</mo> <mn>20</mn> <mo>.</mo> <mn>28</mn> <mspace></mspace> <mtext>mm</mtext></mrow> <annotation>$$ 10.92\kern0.3em \mathrm{mm}\times 20.28\kern0.3em \mathrm{mm} $$</annotation></semantics> </math> , respectively. This work demonstrated the feasibility of the MR-CaDE pulse sequence, which can be used to monitor cavitation events in the brain generated by histotripsy.
Introduction
Purpose
Other
Study Objective
To develop and evaluate an MRI-based method (MR-CaDE) for dynamic cavitation monitoring of histotripsy in ex-vivo brain tissue using a human 3T scanner.
Animal model / Human subject
Ex-vivo bovine brain (Bos taurus); strain: not specified; age: not specified; sex: not specified (tissues sourced from a slaughterhouse, used within 48 h of resection)
Disease model
Healthy
MRI or image guidance method
MRI-guided (MR-CaDE gradient-echo imaging) with array geometric focus estimated using two fiducial markers on the transducer; hydrophone-based aberration correction used for transcranial targeting; post-treatment DWI used to confirm lesion location.
Outcomes and Safety
Summary of Outcomes
MR-CaDE detected focal histotripsy cavitation in ex vivo brain and through human skull samples, with signal changes localized to the focus and lesions confirmed on DWI
Safety-related matter
No thermal effects observed during histotripsy sonications in the ex vivo experiments. As an ex vivo feasibility study, no in vivo tissue safety performed.
Brain Region
Ultrasound Parameters
Ultrasound instrument
Focused 700 kHz, 128-element MR-compatible histotripsy array (focal distance 15 cm; aperture diameter 20.3 cm; f-number 0.74; FWHM 2 × 2 × 7 mm^3)
FUS Frequency
700 kHz
FUS Pressure
70 MPa (peak-negative, free field); 36 MPa (peak-negative, through human skull)
FUS Mode
pulsed
Pulse duration
1.5e-6 s
Focal Characteristics
focal depth: 7 mm; focal length: 15 cm; aperture size: 20.3 cm
Treatment frequency
Multiple sessions
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