Summary of existing preclinical trials
| Model | Frequency (mHz) | Burst length (ms) | Repetition frequency (Hz) | Exposure length (s) | Acoustic pressure (MPa) | Estimated acoustic power (W) | MB type | Therapeutic agent | Observation |
|---|---|---|---|---|---|---|---|---|---|
| Mouse (Swiss Webster) [91] | 0.69 | 10 | 1 | 40 | 0.6–1.1 | - | Optison™ | D4 receptor antibody | Minimal damage seen < 0.8 MPa. Damage observed > 0.8 MPa |
| Mouse (Swiss Webster) [84] | 0.69 | 10 | 1 | 40 | 0.6 and 0.8 | - | Optison™ | Herceptin | Greater delivery at 0.8 MPa compared to 0.6 MPa |
| Transgenic mice (B6C3-Tg and PDAPP) [92] | 0.69 | 10 | 1 | 40–45 | 0.67–0.8 | 0.28–0.4 | Optison™ or Definity® | Anti-amyloid β antibodies | 3-fold increase in antibodies localized to plaques |
| TgCRND8 mice [93] | 0.558 | 10 | 1 | 120 | 0.3 | - | Definity® | Amyloid-β antibodies | Mice treated with MRgFUS had a 12% reduction in plaque sizes |
| non-Tg and TgCRND8 mice [94] | 0.5 | 10 | 1 | 120 | 0.3 | - | Definity® | Endogenous antibodies | Reduced plaque sizes and activation of microglia |
| pR5 mice [95] | 1 | 10 | 10 | 6 | 0.7 | - | In-house lipid-shelled | RN2N antibodies | Mice treated with MRgFUS had an 11-fold increase in RN2N delivery to CNS. Reduced anxiety and tau phosphorylation |
| nu/nu mice (intracranial U87mg cells) [81] | 0.4 | 10 | 1 | 60 | 0.4–0.8 | 4–18 | SonoVue® | Bevacizumab | Animals treated with MRgFUS had decreased tumor growth and vessel area as well as increased survival rates |
| nu/nu mice (intracranial U87mg cells) [83] | 0.5 | 10 | 1 | 60 | 0.3–0.7 | 2–5 | SonoVue® | TMZ | MRgFUS caused TMZ accumulation in the brain to increase and have a slower degradation rate compared to controls. MRgFUS also slowed tumor progression |
| Male NOD-scid mice [88] | 1 | - | 1 | 60 | - | 2.86 | SonoVue® | Doxorubicin | MRgFUS increased oxorubicin concentrations in the brain by 2.35-fold compared with the control tumors |
| C57BL/6J mice [96] | 0.558 | 10 | 1 | 120 | 0.53–0.6 | - | Definity® | Virus serotype 9 | A dose of 2.5 × 109 VG/g allowed expression of the transgene in neurons, astrocytes, and oligodendrocytes in brain regions targeted with ultrasound. Nontargeted regions were minimally infected |
| Athymic nude-Foxn1nu mice [90] | 1.05 | 23.8 | 1 | 120 | 0.3 | - | SonoVue® | Carboplatin | Animals who received MRgFUS had a 4.2-fold increase in carboplatin concentration in the brain. MRgFUS also enhanced survival and delayed tumor growth |
| Nude rats (intracranial M.D. Anderson-metastatic breast (MDA-MB)-361 cells) [85] | 0.69 | 10 | 1 | 60 | 0.46–0.62 | 0.4–0.7 | Optison™ | Trastuzumab and pertuzumab | Animals treated with FUS had slower tumor growth rates and higher survival rates |
| Sprague-Dawley rats (intracranial C6 glioma) [5] | 0.5 | 100 | 1 | 90 | 0.36–0.7 | 5 or 20 | SonoVue® | IL-12 | Animals treated with MRgFUS had a 3-fold increase in IL-12 in the CNS. They also had higher CD8+/T-reg ratio and slower tumor growth |
| Sprague-Dawley rats [97] | 0.55 | 1 | 1 | 120 | 0.24 | - | Definity® | GFP-tagged neural stem cells | MRgFUS allowed higher concentrations of neuronal stem cells in specifically targeted locations in the brain compared to controls |
| Male Sprague-Dawley rats [98] | 1.7 | 10 | 1.7 | 60–120 | 1.2 | - | Optison™ | Doxorubicin | MRgFUS increased the antineoplastic efficacy of liposomal doxorubicin in the brain. Animals treated with FUS had better survival rates compared to controls |
| Male Sprague-Dawley rats [80] | 0.55 | 10 | 1 | 120 | 0.128 and increased by a 0.008/s increment | - | Definity® | Gadovist | MRgFUS induced a transient inflammatory response in microvessels |
| Male Sprague-Dawley rats [87] | 1.5 or 1.7 | 10 | 1 | 30 | 0.36–2.5 | 0.06–3.0 | Optison™ | Doxorubicin | Doxorubicin concentrations were significantly higher in areas targeted by MRgFUS than nontargeted areas of the brain |
| Athymic nude rat (intracranial MDA-MB-231 cells) [99] | 0.55 | 10 | 1 | 120 | 0.32–0.35 | - | Definity® | In HER2-specific NK-92 | 10-fold increase in HER2-specific NK-92 cells regions targeted by MRgFUS |
| Athymic nude rat (intracranial MDA-MB-231 cells) [100] | 0.55 | 10 | 2 | 120 | - | - | Definity® | In HER2-specific NK-92 | Rats with MRgFUS had significantly reduced tumor growth and higher survival rates compared to controls |
| Male Fischer rats [82] | 0.5 | 10 | 1 | 60 | 0.6 | 3 | SonoVue® | TMZ | MRgFUS increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced tumor progression, and increased survival rates |
| Male Sprague-Dawley rats [62] | 0.69 | 10 | 1 | 60 | 0.55 | - | Definity® | Doxorubicin | The concentration of doxorubicin decreased by 32% when injected 10 min after MRgFUS compared to when doxorubicin is injected before sonification |
| Female Sprague-Dawley rats [79] | 0.589 | 10 | 1 | 120 | 0.3 | - | Optison™ | - | MRgFUS increased levels of proinflammatory, anti-inflammatory, trophic, neurotrophic and neurogenesis factors |
| Rabbit (New Zealand white) [55] | 1.63 and 1.5 | 100 | 1 | 20 | - | 0.55 or 3 | Optison™ | - | Sonication as 0.55 W increased the number of endothelial vesicles and fenestrations on the luminal surface of endothelial cells. Damage occurred at 3 W |
| Rabbit (New Zealand white) [89] | 1.1 | - | - | 10 | - | 6 | SonoVue® | Methotrexate | MRgFUS significantly increased methotrexate concentrations in the brain compared to controls |
GFP: green fluorescent protein; HER2: human epithelial growth factor receptor 2; NK: natural killer; NOD: non-obese diabetic; -: none