The developments and applications of functional ultrasound imaging_Journal of Biomedical Engineering

Authors：

HUANG Lijie , HE Qiong , WANG Rui , WEI Xingyue , XIE Gangqiao ,  LUO Jianwen

Department of Biomedical Engineering, Tsinghua University, Beijing 100084, P. R. China;

Corresponding author：

Keywords：

Functional ultrasound imaging; Ultrafast power Doppler imaging; Central nervous system; Brain activation map; Functional connectivity

DOI：

10.7507/1001-5515.202206050

Video：

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In recent years, due to the emergence of ultrafast ultrasound imaging technology, the sensitivity of detecting slow and micro blood flow with ultrasound has been dramatically improved, and functional ultrasound imaging (fUSI) has been developed. fUSI is a novel technology for neurological imaging that utilizes neurovascular coupling to detect the functional activity of the central nervous system (CNS) with high spatiotemporal resolution and high sensitivity, which is dynamic, non-invasive or minimally invasive. fUSI fills the gap between functional magnetic resonance imaging (fMRI) and optical imaging with its high accessibility and portability. Moreover, it is compatible with electrophysiological recording and optogenetics. In this paper, we review the developments of fUSI and its applications in neuroimaging. To date, fUSI has been used in various animals ranging from mice to non-human primates, as well as in clinical surgeries and bedside functional brain imaging of neonates. In conclusion, fUSI has great potential in neuroscience research and is expected to become an important tool for neuroscientists, pathologists and pharmacologists.

Citation： HUANG Lijie, HE Qiong, WANG Rui, WEI Xingyue, XIE Gangqiao, LUO Jianwen. The developments and applications of functional ultrasound imaging. Journal of Biomedical Engineering, 2022, 39(5): 1015-1021. doi: 10.7507/1001-5515.202206050 Copy

1.	Qiu W B, Bouakaz A, Konofagou E E, et al. Ultrasound for the brain: a review of physical and engineering principles, and clinical applications. IEEE Trans Ultrason Ferroelectr Freq Control, 2021, 68(1): 6-20.
2.	Rabut C, Correia M, Finel V, et al. 4D functional ultrasound imaging of whole-brain activity in rodents. Nat Methods, 2019, 16(10): 994-997.
3.	Girouard H, Iadecola C. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol (1985), 2006, 100(1): 328-335.
4.	Tournier N, Comtat C, Lebon V, et al. Challenges and perspectives of the hybridization of pet with functional MRI or ultrasound for neuroimaging. Neuroscience, 2021, 474: 80-93.
5.	齐悦彤, 朱双利. 床旁颅脑超声在不同胎龄早产儿颅脑损伤诊断中的应用. 影像研究与医学应用, 2022, 6(7): 61-63.
6.	Deffieux T, Demené C, Tanter M. Functional Ultrasound Imaging: A New Imaging Modality for Neuroscience. Neuroscience, 2021, 474: 110-121.
7.	Mace E, Montaldo G, Cohen I, et al. Functional ultrasound imaging of the brain. Nat Methods, 2011, 8: 662-664.
8.	Mace E, Montaldo G, Osmanski B F, et al. Functional ultrasound imaging of the brain: theory and basic principles. IEEE Trans Ultrason Ferroelectr Freq Control, 2013, 60(3): 492-506.
9.	Rubin J M, Bude R O, Carson P L, et al. Power Doppler US: a potentially useful alternative to mean frequency-based color Doppler US. Radiology, 1994, 190(3): 853-856.
10.	Montaldo G, Tanter M, Bercoff J, et al. Coherent plane-wave compounding for very high frame rate ultrasonography and transient elastography. IEEE Trans Ultrason Ferroelectr Freq Control, 2009, 56(3): 489-506.
11.	Anzibar Fialho M, Vázquez Alberdi L, Martínez M, et al. Intensity distribution segmentation in ultrafast Doppler combined with scanning laser confocal microscopy for assessing vascular changes associated with ageing in murine hippocampi. Sci Rep, 2022, 12(1): 6784.
12.	Sans-Dublanc A, Chrzanowska A, Reinhard K, et al. Optogenetic fUSI for brain-wide mapping of neural activity mediating collicular-dependent behaviors. Neuron, 2021, 109(11): 1888-1905.
13.	Provansal M, Labernède G, Joffrois C, et al. Functional ultrasound imaging of the spreading activity following optogenetic stimulation of the rat visual cortex. Sci Rep, 2021, 11(1): 12603.
14.	Martinez de Paz J M, Macé E. Functional ultrasound imaging: a useful tool for functional connectomics?. Neuroimage, 2021, 245: 118722.
15.	Blaize K, Arcizet F, Gesnik M, et al. Functional ultrasound imaging of deep visual cortex in awake nonhuman primates. Proc Natl Acad Sci, 2020, 117(25): 14453-14463.
16.	Brunner C, Grillet M, Sans-Dublanc A, et al. A platform for brain-wide volumetric functional ultrasound imaging and analysis of circuit dynamics in awake mice. Neuron, 2020, 108(5): 861-875.
17.	Landemard A, Bimbard C, Demené C, et al. Distinct higher-order representations of natural sounds in human and ferret auditory cortex. eLife, 2021, 10: e65566.
18.	Bergel A, Deffieux T, Demené C, et al. Local hippocampal fast gamma rhythms precede brain-wide hyperemic patterns during spontaneous rodent REM sleep. Nat Commun, 2018, 9(1): 5364.
19.	Bergel A, Tiran E, Deffieux T, et al. Adaptive modulation of brain hemodynamics across stereotyped running episodes. Nat Commun, 2020, 11(1): 6193.
20.	Dizeux A, Gesnik M, Ahnine H, et al. Functional ultrasound imaging of the brain reveals propagation of task-related brain activity in behaving primates. Nat Commun, 2019, 10(1): 1400.
21.	Song P, Cuellar C A, Tang S, et al. Functional ultrasound imaging of spinal cord hemodynamic responses to epidural electrical stimulation: a feasibility study. Front Neurol, 2019, 10: 279.
22.	Tang S, Cuellar C A, Song P, et al. Changes in spinal cord hemodynamics reflect modulation of spinal network with different parameters of epidural stimulation. Neuroimage, 2020, 221: 117183.
23.	Claron J, Hingot V, Rivals I, et al. Large-scale functional ultrasound imaging of the spinal cord reveals in-depth spatiotemporal responses of spinal nociceptive circuits in both normal and inflammatory states. Pain, 2021, 162(4): 1047-1059.
24.	Nayak R, Lee J, Chantigian S, et al. Imaging the response to deep brain stimulation in rodent using functional ultrasound. Phys Med Biol, 2021, 66(5): 05LT01.
25.	Osmanski B F, Pezet S, Ricobaraza A, et al. Functional ultrasound imaging of intrinsic connectivity in the living rat brain with high spatiotemporal resolution. Nat Commun, 2014, 5: 5023.
26.	Rahal L, Thibaut M, Rivals I, et al. Ultrafast ultrasound imaging pattern analysis reveals distinctive dynamic brain states and potent sub-network alterations in arthritic animals. Sci Rep, 2020, 10(1): 10485.
27.	Ferrier J, Tiran E, Deffieux T, et al. Functional imaging evidence for task-induced deactivation and disconnection of a major default mode network hub in the mouse brain. Proc Natl Acad Sci, 2020, 117(26): 15270-15280.
28.	Grohs-Metz G, Smausz R, Gigg J, et al. Functional ultrasound imaging of recent and remote memory recall in the associative fear neural network in mice. Behav Brain Res, 2022, 428: 113862.
29.	Anfray A, Drieu A, Hingot V, et al. Circulating tPA contributes to neurovascular coupling by a mechanism involving the endothelial NMDA receptors. J Cereb Blood Flow Metab, 2020, 40(10): 2038-2054.
30.	Vidal B, Droguerre M, Valdebenito M, et al. Pharmaco-fUS for characterizing drugs for alzheimer's disease - the case of THN201, a drug combination of donepezil plus mefloquine. Front Neurosci, 2020, 14: 835.
31.	Vidal B, Droguerre M, Venet L, et al. Functional ultrasound imaging to study brain dynamics: application of pharmaco-fUS to atomoxetine. Neuropharmacology, 2020, 179: 108273.
32.	Rabut C, Ferrier J, Bertolo A, et al. Pharmaco-fUS: quantification of pharmacologically-induced dynamic changes in brain perfusion and connectivity by functional ultrasound imaging in awake mice. Neuroimage, 2020, 222: 117231.
33.	Norman S L, Maresca D, Christopoulos V N, et al. Single-trial decoding of movement intentions using functional ultrasound neuroimaging. Neuron, 2021, 109(9): 1554-1566.
34.	Orlacchio R, Percherancier Y, Poulletier de Gannes F, et al. In vivo functional ultrasound (fUS) real-time imaging and dosimetry of mice brain under radiofrequency exposure. Bioelectromagnetics, 2022, 43(4): 257-267.
35.	Réaux-Le-Goazigo A, Beliard B, Delay L, et al. Ultrasound localization microscopy and functional ultrasound imaging reveal atypical features of the trigeminal ganglion vasculature. Commun Biol, 2022, 5(1): 330.
36.	Imbault M, Chauvet D, Gennisson J-L, et al. Intraoperative functional ultrasound imaging of human brain activity. Sci Rep, 2017, 7(1): 7304.
37.	Soloukey S, Vincent A J P E, Satoer D D, et al. Functional ultrasound (fUS) during awake brain surgery: the clinical potential of intra-operative functional and vascular brain mapping. Front Neurosci, 2020, 13: 1384.
38.	Demene C, Baranger J, Bernal M, et al. Functional ultrasound imaging of brain activity in human newborns. Sci Transl Med, 2017, 9(411): eaah6756.
39.	Baranger J, Demene C, Frerot A, et al. Bedside functional monitoring of the dynamic brain connectivity in human neonates. Nat Commun, 2021, 12(1): 1080.
40.	Demene C, Robin J, Dizeux A, et al. Transcranial ultrafast ultrasound localization microscopy of brain vasculature in patients. Nat Biomed Eng, 2021, 5(3): 219-228.
41.	Sui Yihui, Yan Shaoyuan, Yu Junjin, et al. Randomized spatial downsampling-based Cauchy-RPCA clutter filtering for high-resolution ultrafast ultrasound microvasculature imaging and functional imaging. IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, 2022, 69(8): 2425-2436.
42.	Sauvage J, Poree J, Rabut C, et al. 4D functional imaging of the rat brain using a large aperture row-column array. IEEE Trans Med Imaging, 2020, 39(6): 1884-1893.
43.	Brunner C, Grillet M, Urban A, et al. Whole-brain functional ultrasound imaging in awake head-fixed mice. Nat Protoc, 2021, 16(7): 3547-3571.

1. Qiu W B, Bouakaz A, Konofagou E E, et al. Ultrasound for the brain: a review of physical and engineering principles, and clinical applications. IEEE Trans Ultrason Ferroelectr Freq Control, 2021, 68(1): 6-20.
2. Rabut C, Correia M, Finel V, et al. 4D functional ultrasound imaging of whole-brain activity in rodents. Nat Methods, 2019, 16(10): 994-997.
3. Girouard H, Iadecola C. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol (1985), 2006, 100(1): 328-335.
4. Tournier N, Comtat C, Lebon V, et al. Challenges and perspectives of the hybridization of pet with functional MRI or ultrasound for neuroimaging. Neuroscience, 2021, 474: 80-93.
5. 齐悦彤, 朱双利. 床旁颅脑超声在不同胎龄早产儿颅脑损伤诊断中的应用. 影像研究与医学应用, 2022, 6(7): 61-63.
6. Deffieux T, Demené C, Tanter M. Functional Ultrasound Imaging: A New Imaging Modality for Neuroscience. Neuroscience, 2021, 474: 110-121.
7. Mace E, Montaldo G, Cohen I, et al. Functional ultrasound imaging of the brain. Nat Methods, 2011, 8: 662-664.
8. Mace E, Montaldo G, Osmanski B F, et al. Functional ultrasound imaging of the brain: theory and basic principles. IEEE Trans Ultrason Ferroelectr Freq Control, 2013, 60(3): 492-506.
9. Rubin J M, Bude R O, Carson P L, et al. Power Doppler US: a potentially useful alternative to mean frequency-based color Doppler US. Radiology, 1994, 190(3): 853-856.
10. Montaldo G, Tanter M, Bercoff J, et al. Coherent plane-wave compounding for very high frame rate ultrasonography and transient elastography. IEEE Trans Ultrason Ferroelectr Freq Control, 2009, 56(3): 489-506.
11. Anzibar Fialho M, Vázquez Alberdi L, Martínez M, et al. Intensity distribution segmentation in ultrafast Doppler combined with scanning laser confocal microscopy for assessing vascular changes associated with ageing in murine hippocampi. Sci Rep, 2022, 12(1): 6784.
12. Sans-Dublanc A, Chrzanowska A, Reinhard K, et al. Optogenetic fUSI for brain-wide mapping of neural activity mediating collicular-dependent behaviors. Neuron, 2021, 109(11): 1888-1905.
13. Provansal M, Labernède G, Joffrois C, et al. Functional ultrasound imaging of the spreading activity following optogenetic stimulation of the rat visual cortex. Sci Rep, 2021, 11(1): 12603.
14. Martinez de Paz J M, Macé E. Functional ultrasound imaging: a useful tool for functional connectomics?. Neuroimage, 2021, 245: 118722.
15. Blaize K, Arcizet F, Gesnik M, et al. Functional ultrasound imaging of deep visual cortex in awake nonhuman primates. Proc Natl Acad Sci, 2020, 117(25): 14453-14463.
16. Brunner C, Grillet M, Sans-Dublanc A, et al. A platform for brain-wide volumetric functional ultrasound imaging and analysis of circuit dynamics in awake mice. Neuron, 2020, 108(5): 861-875.
17. Landemard A, Bimbard C, Demené C, et al. Distinct higher-order representations of natural sounds in human and ferret auditory cortex. eLife, 2021, 10: e65566.
18. Bergel A, Deffieux T, Demené C, et al. Local hippocampal fast gamma rhythms precede brain-wide hyperemic patterns during spontaneous rodent REM sleep. Nat Commun, 2018, 9(1): 5364.
19. Bergel A, Tiran E, Deffieux T, et al. Adaptive modulation of brain hemodynamics across stereotyped running episodes. Nat Commun, 2020, 11(1): 6193.
20. Dizeux A, Gesnik M, Ahnine H, et al. Functional ultrasound imaging of the brain reveals propagation of task-related brain activity in behaving primates. Nat Commun, 2019, 10(1): 1400.
21. Song P, Cuellar C A, Tang S, et al. Functional ultrasound imaging of spinal cord hemodynamic responses to epidural electrical stimulation: a feasibility study. Front Neurol, 2019, 10: 279.
22. Tang S, Cuellar C A, Song P, et al. Changes in spinal cord hemodynamics reflect modulation of spinal network with different parameters of epidural stimulation. Neuroimage, 2020, 221: 117183.
23. Claron J, Hingot V, Rivals I, et al. Large-scale functional ultrasound imaging of the spinal cord reveals in-depth spatiotemporal responses of spinal nociceptive circuits in both normal and inflammatory states. Pain, 2021, 162(4): 1047-1059.
24. Nayak R, Lee J, Chantigian S, et al. Imaging the response to deep brain stimulation in rodent using functional ultrasound. Phys Med Biol, 2021, 66(5): 05LT01.
25. Osmanski B F, Pezet S, Ricobaraza A, et al. Functional ultrasound imaging of intrinsic connectivity in the living rat brain with high spatiotemporal resolution. Nat Commun, 2014, 5: 5023.
26. Rahal L, Thibaut M, Rivals I, et al. Ultrafast ultrasound imaging pattern analysis reveals distinctive dynamic brain states and potent sub-network alterations in arthritic animals. Sci Rep, 2020, 10(1): 10485.
27. Ferrier J, Tiran E, Deffieux T, et al. Functional imaging evidence for task-induced deactivation and disconnection of a major default mode network hub in the mouse brain. Proc Natl Acad Sci, 2020, 117(26): 15270-15280.
28. Grohs-Metz G, Smausz R, Gigg J, et al. Functional ultrasound imaging of recent and remote memory recall in the associative fear neural network in mice. Behav Brain Res, 2022, 428: 113862.
29. Anfray A, Drieu A, Hingot V, et al. Circulating tPA contributes to neurovascular coupling by a mechanism involving the endothelial NMDA receptors. J Cereb Blood Flow Metab, 2020, 40(10): 2038-2054.
30. Vidal B, Droguerre M, Valdebenito M, et al. Pharmaco-fUS for characterizing drugs for alzheimer's disease - the case of THN201, a drug combination of donepezil plus mefloquine. Front Neurosci, 2020, 14: 835.
31. Vidal B, Droguerre M, Venet L, et al. Functional ultrasound imaging to study brain dynamics: application of pharmaco-fUS to atomoxetine. Neuropharmacology, 2020, 179: 108273.
32. Rabut C, Ferrier J, Bertolo A, et al. Pharmaco-fUS: quantification of pharmacologically-induced dynamic changes in brain perfusion and connectivity by functional ultrasound imaging in awake mice. Neuroimage, 2020, 222: 117231.
33. Norman S L, Maresca D, Christopoulos V N, et al. Single-trial decoding of movement intentions using functional ultrasound neuroimaging. Neuron, 2021, 109(9): 1554-1566.
34. Orlacchio R, Percherancier Y, Poulletier de Gannes F, et al. In vivo functional ultrasound (fUS) real-time imaging and dosimetry of mice brain under radiofrequency exposure. Bioelectromagnetics, 2022, 43(4): 257-267.
35. Réaux-Le-Goazigo A, Beliard B, Delay L, et al. Ultrasound localization microscopy and functional ultrasound imaging reveal atypical features of the trigeminal ganglion vasculature. Commun Biol, 2022, 5(1): 330.
36. Imbault M, Chauvet D, Gennisson J-L, et al. Intraoperative functional ultrasound imaging of human brain activity. Sci Rep, 2017, 7(1): 7304.
37. Soloukey S, Vincent A J P E, Satoer D D, et al. Functional ultrasound (fUS) during awake brain surgery: the clinical potential of intra-operative functional and vascular brain mapping. Front Neurosci, 2020, 13: 1384.
38. Demene C, Baranger J, Bernal M, et al. Functional ultrasound imaging of brain activity in human newborns. Sci Transl Med, 2017, 9(411): eaah6756.
39. Baranger J, Demene C, Frerot A, et al. Bedside functional monitoring of the dynamic brain connectivity in human neonates. Nat Commun, 2021, 12(1): 1080.
40. Demene C, Robin J, Dizeux A, et al. Transcranial ultrafast ultrasound localization microscopy of brain vasculature in patients. Nat Biomed Eng, 2021, 5(3): 219-228.
41. Sui Yihui, Yan Shaoyuan, Yu Junjin, et al. Randomized spatial downsampling-based Cauchy-RPCA clutter filtering for high-resolution ultrafast ultrasound microvasculature imaging and functional imaging. IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, 2022, 69(8): 2425-2436.
42. Sauvage J, Poree J, Rabut C, et al. 4D functional imaging of the rat brain using a large aperture row-column array. IEEE Trans Med Imaging, 2020, 39(6): 1884-1893.
43. Brunner C, Grillet M, Urban A, et al. Whole-brain functional ultrasound imaging in awake head-fixed mice. Nat Protoc, 2021, 16(7): 3547-3571.

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The developments and applications of functional ultrasound imaging

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