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Page 12 of 20                                                                                                  Choi et al. Cancer Drug Resist. 2026;9:12





               Table 2. Summary of in vivo and ex vivo US-modulated glymphatic transport studies
               Ref.    Model              Protocol                                   US parameters    Observation

                                          Anesthetized (isoflurane)                  [MB] - None
                                          › ICM inj. of MRI contrast agent           [Transducer]     • Increased uptake into brain parenchyma by 72%-101%
                                          › Pre-US MRI                               • Focused        • Increased residual tracer at 3 h p.i.
                                          › Transcranial US (hair removed; whole brain)  • Fc: 650 kHz
                                          › Post-US MRI (up to 4 h p.i.; 7T, T1w)    • FWHM: 2.78 × 12 mm
               Aryal et  • Rats (male, Long-Evans)
               al. [38]  • Normal                                                    [Sonication]     [FL dye: ~1.5 kDa]
                                          Anesthetized (isoflurane)                  • MI: 0.25       • Higher concentration in brain parenchyma at 1 h p.i.
                                          › ICM inj. of FL-labeled agents (Alexa Fluor 555)  • PNP: 0.2 MPa  [FL-conjugated antibody: ~155 kDa]
                                          › Transcranial US (hair removed; whole brain)  • Duty cycle: 7.7%  • Increased influx into PVS (peak at 1 h p.i.)
                                          › Ex vivo FL micro. (euthanized, tissue fixed, frozen-sectioned)  • Duration:10 min
                                                                                     • Scan area: 8 × 10 mm  • No influx into brain parenchyma
                                          IV inj. of MBs                             [MB]
               Meng et  • Human           › US treatment                             • Commercial     • Reversible BBB opening in all cases
               al. [66]  • AD, ALS        › IV inj. of MRI contrast agent            [Transducer]     • Enhanced contrast in SAS adjacent to sonicated regions
                                          › MRI (0, 24 h p.t.; 3T, T1w/FLAIR)        • Fc: 220 kHz
                                          Anesthetized (isoflurane)
                                          › IN inst. of FL-labeled tracer (Alexa Fluor 555; 24 μL)  [MB]                                                          79
                                          › IV inj. of MB (30 min p.inst.)           • Commercial     • Increased tracer accumulation (1.49× higher FL signal)
                                          › US treatment (hair removed; one side of thalamus)  • Dose: 10 μL/kg  • Enhanced tracer transport in PVS between vessel wall and astrocytic endfeet
                                          › IV inj. of lectin                        [Transducer]     • Arteriole-dominant distribution: 8.75×/5.86× higher FL signal in
                       • Mice (female, NIH Swiss)  › Ex vivo FL imaging (euthanized at 15 min p.t., perfused, brain  • Focused  arterioles/capillaries, with no significant difference in venules
               Ye et al. [63]             sectioned)                                 • Fc: 1.5 MHz    • Increased influx from PVS to IS
                       • Normal
                                          › Ex vivo confocal micro. (optically cleared, immuno-stained:  [Sonication]
                                          lectin/αSMA/GFAP)                          • P: 0.4 MPa
                                                                                     • Pulse length: 6.7 ms
                                          Only changes:                              • PRF: 5 Hz      • Increased tracer accumulation (1.74× higher FL)
                                          › ICM inj. of tracer (5 μL)                • Duration: 60 s  • Arteriole-dominant distribution: 3.49×/2.16×/2.21× higher FL in
                                                                                                      arterioles/capillaries/venules
   81   82   83   84   85   86   87   88   89   90   91