Front. Hum. Neurosci. Frontiers in Human Neuroscience Front. Hum. Neurosci. 1662-5161 Frontiers Media S.A. 10.3389/fnhum.2022.981571 Neuroscience Review A scientometric analysis of the 100 most cited articles on magnetic resonance guided focused ultrasound Garg Kanwaljeet 1 Ranjan Manish 2 * Krishna Vibhor 3 Singh Manmohan 1 Rezai Ali 2 1All India Institute of Medical Sciences, New Delhi, India 2Department of Neurosurgery, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, United States 3The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

Edited by: Nan-kuei Chen, University of Arizona, United States

Reviewed by: Gregory Noetscher, Combat Capabilities Development Command United States Army, United States; Francesca Di Giuliano, University of Rome Tor Vergata, Italy

 *Correspondence: Manish Ranjan, drmanishranjan@gmail.com

This article was submitted to Brain Imaging and Stimulation, a section of the journal Frontiers in Human Neuroscience

 12 09 2022 2022 16 981571 29 06 2022 15 08 2022 Copyright © 2022 Garg, Ranjan, Krishna, Singh and Rezai. 2022 Garg, Ranjan, Krishna, Singh and Rezai

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 Background

Diagnostic ultrasound has long been a part of a physician’s armamentarium, but transcranial focused ultrasound (FUS) is an emerging treatment of neurological disorders. Consequently, the literature in this field is increasing at a rapid pace.

 Objective

This analysis was aimed to identify the top-cited articles on FUS to discern their origin, spread, current trends highlighting future impact of this novel neurosurgical intervention.

 Methods

We searched the Web of Science database on 28th May 2021 and identified the top 100 cited articles. These articles were analyzed with various scientometric parameters like the authors, corresponding authors, country of corresponding author, journal of publication, year of publication. Citation based parameters including total citations, mean citations per article and mean citations, citation count, and the citation per year, citations per year and co-authors per document were studied as well in addition to Hirsch h-index, g-index, m-index, Bradford’s Law, Lotka’s law and Collaboration index.

 Results

The 100 top-cited articles were published between 1998 and 2019 in 45 different journals. The average citations per document and citations per document per year were 97.78 and 12.47, respectively. The most prolific authors were Hynynen K (Medical Biophysics—Toronto), Elias WJ (Neurosurgery—Virginia), Zadicario (InSightec). The Journal of Neurosurgery published the most top-cited articles (n = 11), and most articles originated from the United States, followed by Canada. Among individual institutions, the University of Toronto was the most productive.

 Conclusion

FUS is an emerging treatment of neurological disorders. With its increasing application, the FUS literature is increasing rapidly. Eleven countries contributed to the top 100 cited articles, with the top 2 countries (the United States and Canada) contributing to more than half of these articles.

 focused ultrasound neurosurgery Parkinson’s disease essential tremor MRI FUS Introduction

Diagnostic ultrasound has been a part of a physician’s armamentarium for the last seven decades. Focsused ultrasound (FUS) has emerged as a therapeutic option in the last few decades to successfully ablate soft tissue tumors such as uterine fibroids, breast carcinoma, and bone metastases (Fry et al., 1958; Fry and Fry, 1960; Cline et al., 1992, 1993, 1995; Hynynen et al., 1993a,b). Technological advances including development of a phased spherical array with a multielement transducer helmet and the implementation of magnetic resonance imaging guidance for real-time tissue temperature monitoring led to intracranial application for neurological disorders, specifically the movement disorders (Clement and Hynynen, 2002; Lipsman et al., 2014). FUS has evolved rapidly in the recent years, specifically in the functional neurosurgery with significant clinical and research publication.

Bibliometrics is a methodological approach from the library sciences that statistically analyses the citation counts of books, articles, and other publications to determine the influence and impact of the scientific publications. Scientometrics is a subfield of bibliometrics that studies science publications by using bibliometric methods to find author, article, and journal-level metrics (i.e., H-index, citation index, and journal impact factor, respectively). It provides a broad overview of the field’s direction, complements the expert peer review process, and is transparent and objective. Many scientometric analyses have been published in neurosurgery to find the 100-most cited articles on topics like endoscopic third ventriculostomy, ossified posterior longitudinal ligament, pallidotomy, and cervical spondylotic myelopathy (Zagzoog et al., 2018; Chen et al., 2019; Agrawal et al., 2021; Garg et al., 2021, 2022a,b; Zhao et al., 2021). However, there is no such article published on transcranial FUS. This scientometric analysis presents the top 100 cited articles published on transcranial FUS and further reports the most significant contributors (authors, institutes, and countries) along with the various scientometric indices.

 Materials and methods Search strategy

A systematic search of the Web of Science database was performed on 28th May 2021. The keywords used for literature search were—“MR guided focused ultrasound,” “MRgFUS,” “Magnetic resonance-guided focused ultrasound,” “Ultrasound Thalamotomy,” “Ultrasound Thalamotomy for Essential Tremor,” “Ultrasound Subthalamotomy, “focused ultrasound tremor,” “focused ultrasound tremor,” “ultrasound Parkinson,” “focused ultrasound ablation,” “transcranial focused ultrasound,” “focused ultrasound neuromodulation” and “focused ultrasound blood brain barrier opening.” The search results were screened and arranged in descending order of the number of citations, and articles were selected as per the following inclusion and exclusion criteria. FUS studies on transcranial FUS for neurological disorders, comparative study of FUS with DBS or radiofrequency (RF) for movement disorders, blood-brain barrier permeability, animal or cadaver research, targeted therapeutics and radiological aspect of FUS were included. FUS articles on non-cranial pathology were excluded.

 Data and bibliometric parameters studied

The articles were arranged in descending order according to the number of citations. The various parameters analyzed were the title of the articles, authors, corresponding authors, country of corresponding author, journal of publication, year of publication. Citation based parameters including total citations, mean citations per article and mean citations, citation count, and the citation per year, citations per year and co-authors per document were studied as well. The following statistical parameters were considered during the analysis:

Hirsch h-index: authors number of publications and number of citations, reviewed in other articles.

g-index: is a variant of h-index which gives credit for the most cited papers. It is the highest rank where the sum of the citations is larger than the square of rank.

m-index: is another variant of the h-index that displays h-index per year since first publication.

Bradford’s Law: estimates the exponentially diminishing returns of searching for references in science journals was also studied.

Lotka’s law: which denotes the distribution of the number of articles published by the number of authors.

Collaboration index: it assigns a weighted credit to each author in a multi-author paper to capture a researcher’s scientific caliber better.

 Analysis

The statistical analysis was performed using R software version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria) (Aria and Cuccurullo, 2017; R Core Team, 2022).

 Results Articles

The literature search yielded 2,500 articles, and we selected the 100 most cited articles which met the study inclusion and exclusion criteria (Hynynen et al., 2001, 2006; McDannold et al., 2005, 2010; Jordão et al., 2010; Bystritsky et al., 2011; Yoo et al., 2011; Jeanmonod et al., 2012; Park et al., 2012; Treat et al., 2012; Fan et al., 2013; Nance et al., 2014; Elias et al., 2016; Kovacs et al., 2017; Mainprize et al., 2019; Alzheimer’s disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior—PubMed). The included top-cited articles are summarized in Table 1.

Summary of the included articles.

Paper DOI Article type Journal Publication year Corresponding author University of corresponding author Total citations TC peryear Normalized TC Type ofstudy Theme ofstudy Title ofarticle
HYNYNEN K, 2001, RADIOLOGY 10.1148/radiol.2202001804 ARTICLE RADIOLOGY 2001 HYNYNEN, K HARVARD UNIV, USA, USA 855 40.71 1 Animal Blood-brain barrier Noninvasive MR imaging–guided focal opening of the blood-brain barrier in rabbits
ELIAS WJ, 2013, NEW ENGL J MED 10.1056/NEJMoa1300962 ARTICLE NEW ENGL J MED 2013 ELIAS, WJ UNIV VIRGINIA, 385 42.78 2.984 Human Movement disorder A pilot study of focused ultrasound thalamotomy for essential tremor
ELIAS WJ, 2016, NEW ENGL J MED 10.1056/NEJMoa1600159 ARTICLE NEW ENGL J MED 2016 ELIAS, WJ UNIV VIRGINIA, 376 62.67 3.547 Human Movement disorder A randomized trial of focused ultrasound thalamotomy for essential tremor
MCDANNOLD N, 2010, NEUROSURGERY 10.1227/01.NEU.0000360379.95800.2F ARTICLE NEUROSURGERY 2010 MCDANNOLD, N HARVARD UNIV,USA 360 30 2.059 Human Oncology Transcranial magnetic resonance imaging– guided focused ultrasound surgery of brain tumors: initial findings in 3 patients
LIPSMAN N, 2013, LANCET NEUROL 10.1016/S1474-4422(13)70048-6 ARTICLE LANCET NEUROL 2013 LOZANO, AM UNIV TORONTO, CANADA 310 34.44 2.403 Human Movement disorder MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study
MARTIN E, 2009, ANN NEUROL 10.1002/ana.21801 ARTICLE ANN NEUROL 2009 MARTIN, E UNIV CHILDRENS HOSP ZURICH, 286 22 2.424 Human Pain High-intensity focused ultrasound for noninvasive functional neurosurgery
LIU HL, 2010, P NATL ACAD SCI USA 10.1073/pnas.1003388107 ARTICLE P NATL ACAD SCI USA 2010 CHEN, PY CHANG GUNG UNIV, COLL MED 282 23.5 1.613 Review - Animal Blood-brain barrier Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain
YOO SS, 2011, NEUROIMAGE 10.1016/j.neuroimage.2011.02.058 ARTICLE NEUROIMAGE 2011 YOO, SS HARVARD UNIV, USA 265 24.09 1.205 Animal Stimulation Focused ultrasound modulates region-specific brain activity
HYNYNEN K, 2006, J NEUROSURG 10.3171/jns.2006.105.3.445 ARTICLE J NEUROSURG 2006 HYNYNEN, K UNIV TORONTO, CANADA 231 14.44 1.351 Animal Blood-brain barrier Focal disruption of the blood–brain barrier due to 260-kHz ultrasound bursts: a method for molecular imaging and targeted drug delivery
MCDANNOLD N, 2005, ULTRASOUND MED BIOL 10.1016/j.ultrasmedbio.2005.07.010 ARTICLE ULTRASOUND MED BIOL 2005 MCDANNOLD, N HARVARD UNIV,USA, USA 225 13.24 1 Animal Blood-brain barrier MRI-guided targeted blood-brain barrier disruption with focused ultrasound: Histological findings in rabbits
JORDAO JF, 2010, PLOS ONE 10.1371/journal.pone.0010549 ARTICLE PLOS ONE 2010 JORDAO, JF SUNNYBROOK RES INST, TORONTO 221 18.42 1.264 Animal Alzheimer’s disease Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-beta plaque load in the TgCRND8 mouse model of Alzheimer’s disease
LIPSMAN N, 2018, NAT COMMUN 10.1038/s41467-018-04529-6 ARTICLE NAT COMMUN 2018 SUNNYBROOK RES INST UNIV TORONTO, CANADA 213 53.25 3.252 Human Alzheimer’s disease Blood–brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound
JEANMONOD D, 2012, NEUROSURG FOCUS 10.3171/2011.10.FOCUS11248 ARTICLE NEUROSURG FOCUS 2012 JEANMONOD, D CTR ULTRASOUND FUNCT NEUROSURG, SWITZERLAND. 195 19.5 2.27 Human Pain Transcranial magnetic resonance imaging–guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain
BYSTRITSKY A, 2011, BRAIN STIMUL 10.1016/j.brs.2011.03.007 REVIEW BRAIN STIMUL 2011 BYSTRITSKY, A UNIV CALIF LOS ANGELES, LOS ANGELES, USA 175 15.91 0.795 Human Neurostimulation A review of low-intensity focused ultrasound pulsation
FAN CH, 2013, BIOMATERIALS 10.1016/j.biomaterials.2013.01.099 ARTICLE BIOMATERIALS 2013 YEH, CK NATL TSING HUA UNIV, TAIWAN 158 17.56 1.225 Animal Blood-brain barrier SPIO-conjugated, doxorubicin-loaded microbubbles for concurrent MRI and focused-ultrasound enhanced brain-tumor drug delivery
TREAT LH, 2012, ULTRASOUND MED BIOL 10.1016/j.ultrasmedbio.2012.04.015 ARTICLE ULTRASOUND MED BIOL 2012 MCDANNOLD, N HARVARD UNIV, USA, USA 158 15.8 1.84 Animal Blood-brain barrier Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by mri-guided focused ultrasound in rat glioma
HYNYNEN K, 2006, EUR J RADIOL 10.1016/j.ejrad.2006.04.007 ARTICLE EUR J RADIOL 2006 HYNYNEN, K HARVARD UNIV, USA, USA 157 9.81 0.918 Animal Technique Pre-clinical testing of a phased array ultrasound system for MRI-guided noninvasive surgery of the brain–a primate study
KOVACS ZI, 2017, P NATL ACAD SCI USA 10.1073/pnas.1614777114 ARTICLE P NATL ACAD SCI USA 2017 KOVACS, ZI NIH, FRANK LAB, RADIOL & IMAGING SCI, US 143 28.6 2.566 Animal Blood-brain barrier Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation
NANCE E, 2014, J CONTROL RELEASE 10.1016/j.jconrel.2014.06.031 ARTICLE J CONTROL RELEASE 2014 PRICE, RJ UNIV VIRGINIA, USA 131 16.38 2.012 Animal Blood-brain barrier Non-invasive delivery of stealth, brain-penetrating nanoparticles across the blood-brain barrier using MRI-guided focused ultrasound
BURGESS A, 2014, RADIOLOGY 10.1148/radiol.14140245 ARTICLE RADIOLOGY 2014 BURGESS, A SUNNYBROOK RES INST, TORONTO 130 16.25 1.997 Animal Alzheimer’s disease Alzheimer’s disease in a mouse model: MR imaging–guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior
MAINPRIZE T, 2019, SCI REP-UK 10.1038/s41598-018-36340-0 ARTICLE SCI REP-UK 2019 MAINPRIZE, T SUNNYBROOK HLTH SCI CTR, CANADA 129 43 2.449 Human Oncology Blood-brain barrier opening in primary brain tumors with non-invasive MR-guided focused ultrasound: a clinical safety and feasibility study
RAM Z, 2006, NEUROSURGERY 10.1227/01.NEU.0000254439.02736.D8 ARTICLE NEUROSURGERY 2006 RAM, Z TEL AVIV SOURASKY MED CTR, ISRAEL 125 7.81 0.731 Human Oncology Magnetic resonance imaging-guided, high-intensity focused ultrasound for brain tumor therapy
PARK EJ, 2012, J CONTROL RELEASE 10.1016/j.jconrel.2012.09.007 ARTICLE J CONTROL RELEASE 2012 PARK, EJ HARVARD UNIV, USA, USA 113 11.3 1.316 Animal Blood-brain barrier Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model
LEINENGA G, 2016, NAT REV NEUROL 10.1038/nrneurol.2016.13 REVIEW NAT REV NEUROL 2016 GOTZ, J UNIV QUEENSLAND, AUSTRALIA 109 18.17 1.028 Review Ultrasound treatment of neurological diseases — current and emerging applications
CHANG WS, 2015, J NEUROL NEUROSUR PS 10.1136/jnnp-2014-307642 ARTICLE J NEUROL NEUROSUR PS 2015 CHANG, JW YONSEI UNIV, SOUTH KOREA 109 15.57 1.697 Human Movement disorder Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes
OBESO JA, 2017, MOVEMENT DISORD 10.1002/mds.27115 REVIEW MOVEMENT DISORD 2017 OBESO, JA HOSP UNIV HM PUERTA SUR, SPAIN 102 20.4 1.83 Review Movement disorder Past, present, and future of Parkinson’s disease: a special essay on the 200th anniversary of the shaking palsy
MCDANNOLD N, 2007, ULTRASOUND MED BIOL 10.1016/j.ultrasmedbio.2006.10.004 ARTICLE ULTRASOUND MED BIOL 2007 MCDANNOLD, N BRIGHAM & WOMENS HOSP, USA 96 6.4 1.401 Animal Blood-brain barrier Use of ultrasound pulses combined with definity for targeted blood-brain barrier disruption: a feasibility study
JUNG HH, 2015, MOL PSYCHIATR 10.1038/mp.2014.154 ARTICLE MOL PSYCHIATR 2015 KIM, CH INST BEHAV SCI MED, SOUTH KOREA 88 12.57 1.37 Human OCD Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study
BOND AE, 2017, JAMA NEUROL 10.1001/jamaneurol.2017.3098 ARTICLE JAMA NEUROL 2017 ELIAS, WJ UNIV VIRGINIA, USA 87 17.4 1.561 Human Movement disorder Safety and efficacy of focused ultrasound thalamotomy for patients with medication-refractory, tremor-dominant Parkinson’s disease
SUN T, 2017, P NATL ACAD SCI USA 10.1073/pnas.1713328114 ARTICLE P NATL ACAD SCI USA 2017 SUN, T HARVARD UNIV, USA, USA 87 17.4 1.561 Animal Blood-brain barrier Closed-loop control of targeted ultrasound drug delivery across the blood–brain/tumor barriers in a rat glioma model
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ZAAROOR M, 2018, J NEUROSURG 10.3171/2016.10.JNS16758 ARTICLE J NEUROSURG 2018 ZAAROOR, M RAMBAM HLTH CARE CAMPUS, ISRAEL 80 20 1.221 Human Movement disorder Magnetic resonance-guided focused ultrasound thalamotomy for tremor: a report of 30 Parkinson’s disease and essential tremor cases
MARSAC L, 2012, MED PHYS 10.1118/1.3678988 ARTICLE MED PHYS 2012 MARSAC, L UNIV PARIS, FRANCE 79 7.9 0.92 Human Technique MR-guided adaptive focusing of therapeutic ultrasound beams in the human head
MEI J, 2009, J ULTRAS MED 10.7863/jum.2009.28.7.871 ARTICLE J ULTRAS MED 2009 CHENG, Y CHONGQING MED UNIV, PEOPLES R CHINA 76 5.85 0.644 Animal Blood-brain barrier Experimental study on targeted methotrexate delivery to the rabbit brain via magnetic resonance imaging–guided focused ultrasound
JAGANNATHAN J, 2009, NEUROSURGERY 10.1227/01.NEU.0000336766.18197.8E REVIEW NEUROSURGERY 2009 KASSELL, NF UNIV VIRGINIA, USA 76 5.85 0.644 Review High-intensity focused ultrasound surgery of the brain: part 1—a historical perspective with modern applications
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GHANOUNI P, 2015, AM J ROENTGENOL 10.2214/AJR.14.13632 REVIEW AM J ROENTGENOL 2015 WINTERMARK, M STANFORD UNIV, USA 71 10.14 1.106 Review Transcranial MRI-guided focused ultrasound: a review of the technologic and neurologic applications
SCARCELLI T, 2014, BRAIN STIMUL 10.1016/j.brs.2013.12.012 ARTICLE BRAIN STIMUL 2014 HYNYNEN, K UNIV TORONTO, CANADA 70 8.75 1.075 Animal Alzheimer’s disease Stimulation of hippocampal neurogenesis by transcranial focused ultrasound and microbubbles in adult mice
KONOFAGOU EE, 2012, CURR PHARM BIOTECHNO NA REVIEW CURR PHARM BIOTECHNO 2012 KONOFAGOU, EE COLUMBIA UNIV, USA 70 7 0.815 Review Blood-brain barrier Ultrasound-induced blood-brain barrier opening
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FAN CH, 2016, THERANOSTICS 10.7150/thno.15297 ARTICLE THERANOSTICS 2016 YEH, CK NATL TSING HUA UNIV, TAIWAN 64 10.67 0.604 Animal Blood-brain barrier Ultrasound/magnetic targeting with SPIO-DOX-microbubble complex for image-guided drug delivery in brain tumors
KRISHNA V, 2018, JAMA NEUROL 10.1001/jamaneurol.2017.3129 REVIEW JAMA NEUROL 2018 KRISHNA, V OHIO STATE UNIV, USA 63 15.75 0.962 Review A review of the current therapies, challenges, and future directions of transcranial focused ultrasound technology
WINTERMARK M, 2014, AM J NEURORADIOL 10.3174/ajnr.A3808 ARTICLE AM J NEURORADIOL 2014 WINTERMARK, M UNIV VIRGINIA, USA 63 7.88 0.968 Human Movement disorder Imaging findings in MR imaging–guided focused ultrasound treatment for patients with essential tremor
FAN CH, 2016, SCI REP-UK 10.1038/srep19579 ARTICLE SCI REP-UK 2016 LIU HL CHANG GUNG UNIV, TAIWAN 62 10.33 0.585 Animal Blood-brain barrier Noninvasive, targeted and non-viral ultrasound-mediated GDNF-plasmid delivery for treatment of Parkinson’s disease
HUSS DS, 2015, MOVEMENT DISORD 10.1002/mds.26455 ARTICLE MOVEMENT DISORD 2015 ELIAS, WJ UNIV VIRGINIA, USA 60 8.57 0.934 Human Movement disorder Functional assessment and quality of life in essential tremor with bilateral or unilateral DBS and focused ultrasound thalamotomy
HUANG Q, 2012, EXP NEUROL 10.1016/j.expneurol.2011.10.027 ARTICLE EXP NEUROL 2012 CHENG, Y CHONGQING MED UNIV, PEOPLES R CHINA 58 5.8 0.675 Animal Blood-brain barrier Targeted gene delivery to the mouse brain by MRI-guided focused ultrasound-induced blood–brain barrier disruption
SAMIOTAKI G, 2015, J CEREBR BLOOD F MET 10.1038/jcbfm.2014.236 ARTICLE J CEREBR BLOOD F MET 2015 KONOFAGOU, EE COLUMBIA UNIV, USA 57 8.14 0.888 Animal Blood-brain barrier Enhanced delivery and bioactivity of the neurturin neurotrophic factor through focused ultrasound—mediated blood—brain barrier opening in vivo
CHANG JW, 2018, ANN NEUROL 10.1002/ana.25126 ARTICLE ANN NEUROL 2018 CHANG, JW YONSEI UNIV, SOUTH KOREA 55 13.75 0.84 Human Movement disorder A prospective trial of magnetic resonance–guided focused ultrasound thalamotomy for essential tremor: results at the 2-year follow-up
JONES RM, 2018, THERANOSTICS 10.7150/thno.24911 ARTICLE THERANOSTICS 2018 JONES, RM SUNNYBROOK RES INST, CANADA 55 13.75 0.84 Animal Blood-brain barrier Three-dimensional transcranial microbubble imaging for guiding volumetric ultrasound-mediated blood-brain barrier opening
KYRIAKOU A, 2014, INT J HYPERTHER 10.3109/02656736.2013.861519 REVIEW INT J HYPERTHER 2014 KYRIAKOU, A ITIS FDN RES INFORMAT TECHNOL SOC, SWITZERLAND 55 6.88 0.845 Review A review of numerical and experimental compensation techniques for skull-induced phase aberrations in transcranial focused ultrasound
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SCHLESINGER I, 2015, PARKINSONS DIS-US 10.1155/2015/219149 ARTICLE PARKINSONS DIS-US 2015 SCHLESINGER, I RAMBAM HLTH CARE CAMPUS, ISRAEL 54 7.71 0.841 Human Movementdisorder MRI guided focused ultrasound thalamotomy for moderate-to-severe tremor in Parkinson’s disease
DIAZ RJ, 2014, NANOMED-NANOTECHNOL 10.1016/j.nano.2013.12.006 ARTICLE NANOMED-NANOTECHNOL 2014 RUTKA, JT UNIV TORONTO, CANADA, CANADA 54 6.75 0.829 In vivo Blood-brainbarrier Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: potential for targeting experimental brain tumors
DEFFIEUX T, 2010, IEEE T ULTRASON FERR 10.1109/TUFFC.2010.1738 ARTICLE IEEE T ULTRASON FERR 2010 DEFFIEUX, T COLUMBIA UNIV, USA 54 4.5 0.309 Animal and Human skulls Blood-brainbarrier Numerical study of a simple transcranial focused ultrasound system applied to blood-brain barrier opening
LEGON W, 2018, HUM BRAIN MAPP 10.1002/hbm.23981 ARTICLE HUM BRAIN MAPP 2018 LEGON, W UNIV VIRGINIA, USA 53 13.25 0.809 Human Neuromodulation Neuromodulation with single-element transcranial focused ultrasound in human thalamus
MEAD BP, 2017, NANO LETT 10.1021/acs.nanolett.7b00616 ARTICLE NANO LETT 2017 HANES, J; PRICE, RJ JOHNS HOPKINS UNIV, USA; UNIV VIRGINIA, USA 52 10.4 0.933 Animal Blood-brainbarrier Novel focused ultrasound gene therapy approach noninvasively restores dopaminergic neuron function in a rat Parkinson’s disease model
LIN CY, 2016, J CONTROL RELEASE 10.1016/j.jconrel.2016.05.052 ARTICLE J CONTROL RELEASE 2016 LIU, HL CHANG GUNG UNIV, TAIWAN 51 8.5 0.481 Animal Blood-brainbarrier Non-invasive, neuron-specific gene therapy by focused ultrasound-induced blood-brain barrier opening in Parkinson’s disease mouse model
ELIAS WJ, 2013, J NEUROSURG 10.3171/2013.5.JNS122327 ARTICLE J NEUROSURG 2013 ELIAS, WJ UNIV VIRGINIA, USA 51 5.67 0.395 Animal Lesion size A magnetic resonance imaging, histological, and dose modeling comparison of focused ultrasound, radiofrequency, and Gamma Knife radiosurgery lesions in swine thalamus
SUN T, 2015, PHYS MED BIOL 10.1088/0031-9155/60/23/9079 ARTICLE PHYS MED BIOL 2015 SUN, T HARVARD UNIV, USA, USA 50 7.14 0.779 Animal Blood-brainbarrier Acoustic cavitation-based monitoring of the reversibility and permeability of ultrasound-induced blood-brain barrier opening
MCDANNOLD N, 2003, MAGNET RESON MED 10.1002/mrm.10453 ARTICLE MAGNET RESON MED 2003 MCDANNOLD, N BRIGHAM & WOMENS HOSP, USA 48 2.53 1 Animal Technique MRI-guided focused ultrasound surgery in the brain: tests in a primate model
BOUTET A, RANJAN M, 2018, BRAIN 10.1093/brain/awy278 ARTICLE BRAIN 2018 LOZANO, AM UNIV TORONTO, CANADA, CANADA 47 11.75 0.718 Human Movement disorder Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor
TIMBIE KF, 2017, J CONTROL RELEASE 10.1016/j.jconrel.2017.03.017 ARTICLE; PROCEEDINGS PAPER J CONTROL RELEASE 2017 PRICE, RJ UNIV VIRGINIA, USA 46 9.2 0.825 Animal Blood-brain barrier MR image-guided delivery of cisplatin-loaded brain-penetrating nanoparticles to invasive glioma with focused ultrasound
JUNG HH, 2015, J NEUROSURG 10.3171/2014.8.JNS132603 ARTICLE J NEUROSURG 2015 CHANG, JW YONSEI UNIV, SOUTH KOREA 45 6.43 0.701 Human Movement disorder Different magnetic resonance imaging patterns after transcranial magnetic resonance–guided focused ultrasound of the ventral intermediate nucleus of the thalamus and anterior limb of the internal capsule in patients with essential tremor or obsessive-compulsive disorder
NA YC, 2015, NEUROLOGY 10.1212/WNL.0000000000001826 EDITORIAL MATERIAL NEUROLOGY 2015 CHANG, JW YONSEI UNIV, SOUTH KOREA 44 6.29 0.685 Human Movement disorder Unilateral magnetic resonance–guided focused ultrasound pallidotomy for Parkinson’s disease
CHAUVET D, 2013, J NEUROSURG 10.3171/2013.1.JNS12559 ARTICLE J NEUROSURG 2013 AUBRY, JF ESPCI, INST LANGEVIN, FRANCE 43 4.78 0.333 Human Technique Targeting accuracy of transcranial magnetic resonance-guided high-intensity focused ultrasound brain therapy: a fresh cadaver model
HUANG YX, 2017, RADIOLOGY 10.1148/radiol.2016152154 ARTICLE RADIOLOGY 2017 HUANG, YX SUNNYBROOK RES INST, CANADA 42 8.4 0.754 Human Blood-brain barrier Opening the blood-brain barrier with MR imaging–guided focused ultrasound: preclinical testing on a trans–human skull porcine model
CHAZEN JL, 2018, J NEUROSURG 10.3171/2017.4.JNS162803 ARTICLE J NEUROSURG 2018 CHAZEN, JL Weill Cornell Medicine, USA 41 10.25 0.626 Human Movement disorder Clinical improvement associated with targeted interruption of the cerebellothalamic tract following MR-guided focused ultrasound for essential tremor
COHEN ZR, 2007, NEUROSURGERY 10.1227/01.NEU.0000245606.99946.C6 ARTICLE NEUROSURGERY 2007 RAM, Z TEL AVIV MED CTR & SCH MED, ISRAEL 41 2.73 0.599 Animal Technique Magnetic resonance imaging-guided focused ultrasound for thermal ablation in the brain: a feasibility study in a swine model
COLUCCIA D, 2018, NANOMED-NANOTECHNOL 10.1016/j.nano.2018.01.021 ARTICLE NANOMED-NANOTECHNOL 2018 RUTKA, JT HOSP SICK CHILDREN, CANADA 40 10 0.611 Animal Blood-brain barrier Enhancing glioblastoma treatment using cisplatin-gold-nanoparticle conjugates and targeted delivery with magnetic resonance-guided focused ultrasound
MONTEITH SJ, 2013, J NEUROSURG-a 10.3171/2012.12.JNS121095 ARTICLE J NEUROSURG 2013 MONTEITH, S UNIV VIRGINIA, USA 40 4.44 0.31 Animal ICH Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance–guided focused ultrasound
LIPSMAN N, 2014, NEUROTHERAPEUTICS 10.1007/s13311-014-0281-2 REVIEW NEUROTHERAPEUTICS 2014 LIPSMAN, N UNIV TORONTO, CANADA, CANADA 39 4.88 0.599 Review Intracranial applications of magnetic resonance-guidedfocused ultrasound
PULKKINEN A, 2014, PHYS MED BIOL 10.1088/0031-9155/59/7/1679 ARTICLE PHYS MED BIOL 2014 PULKKINEN, A UNIV EASTERN FINLAND, FINLAND 39 4.88 0.599 Human Technique Numerical simulations of clinical focused ultrasound functional neurosurgery
RAVIKUMAR VK, 2017, MOVEMENT DISORD 10.1002/mds.26997 ARTICLE MOVEMENT DISORD 2017 HALPERN, CH STANFORD UNIV, USA 38 7.6 0.682 Human Movement disorder Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor
WINTERMARK M, 2014, RADIOLOGY 10.1148/radiol.14132112 ARTICLE RADIOLOGY 2014 WINTERMARK, M UNIV VIRGINIA, USA 37 4.62 0.568 Human Movement disorder Thalamic connectivity in patients with essential tremor treated with MR imaging–guided focused ultrasound: in vivo fiber tracking by using diffusion-tensor MR imaging
MEDEL R, 2012, NEUROSURGERY 10.1227/NEU.0b013e3182672ac9 REVIEW NEUROSURGERY 2012 KASSELL, NF UNIV VIRGINIA, USA 37 3.7 0.431 Review Magnetic resonance–guided focused ultrasound surgery: Part 2: a review of current and future applications
FAN CH, 2017, J CONTROL RELEASE 10.1016/j.jconrel.2017.07.004 REVIEW J CONTROL RELEASE 2017 YEH, CK NATL TSING HUA UNIV, TAIWAN 36 7.2 0.646 Review Ultrasound targeted CNS gene delivery for Parkinson’s disease treatment
DEVARAKONDA SB, 2017, NANO LETT 10.1021/acs.nanolett.7b00272 ARTICLE NANO LETT 2017 BANERJEE, RK UNIV CINCINNATI, USA 36 7.2 0.646 Phantom Technique Assessment of gold nanoparticle-mediated-enhanced hyperthermia using MR-guided high-intensity focused ultrasound ablation procedure
ALLI S, 2018, J CONTROL RELEASE 10.1016/j.jconrel.2018.05.005 ARTICLE J CONTROL RELEASE 2018 RUTKA, JT HOSP SICK CHILDREN, CANADA 35 8.75 0.534 Animal Blood-brain barrier Brainstem blood brain barrier disruption using focused ultrasound: a demonstration of feasibility and enhanced doxorubicin delivery
O’REILLY MA, 2017, J ULTRAS MED 10.7863/ultra.16.02005 ARTICLE J ULTRAS MED 2017 O’REILLY, MA SUNNYBROOK RES INST, CANADA 35 7 0.628 Animal Blood-brain barrier Blood-brain barrier closure time after controlled ultrasound-induced opening is independent of opening volume
MOROCZ IA, 1998, J MAGN RESON IMAGING 10.1002/jmri.1880080126 ARTICLE J MAGN RESON IMAGING 1998 JOLESZ, FA HARVARD UNIV, USA, USA 35 1.46 1 Animal Complications Brain edema development after MRI-guided focused ultrasound treatment
WANG F, 2009, J ULTRAS MED 10.7863/jum.2009.28.11.1501 ARTICLE J ULTRAS MED 2009 CHENG, Y CHONGQING MED UNIV, PEOPLES R CHINA 34 2.62 0.288 Animal Blood-brain barrier Focused ultrasound microbubble destruction-mediated changes in blood-brain barrier permeability assessed by contrast-enhanced magnetic resonance imaging
FASANO A, 2017, NEUROLOGY 10.1212/WNL.0000000000004268 ARTICLE NEUROLOGY 2017 FASANO, A UNIV TORONTO, CANADA, CANADA 33 6.6 0.592 Human Movement disorder MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes
KIM M, 2017, STEREOT FUNCT NEUROS 10.1159/000478866 ARTICLE STEREOT FUNCT NEUROS 2017 CHANG, JW YONSEI UNIV, SOUTH KOREA 33 6.6 0.592 Human Movement disorder Comparative evaluation of magnetic resonance-guided focused ultrasound surgery for essential tremor
O’REILLY MA, 2017, THERANOSTICS 10.7150/thno.20621 ARTICLE THERANOSTICS 2017 O’REILLY, MA SUNNYBROOK RES INST, CANADA 33 6.6 0.592 Animal Blood-brain barrier Investigation of the safety of focused ultrasound-induced blood-brain barrier opening in a natural canine model of aging
WEINTRAUB D, 2017, MOVEMENT DISORD 10.1002/mds.26599 REVIEW MOVEMENT DISORD 2017 ELIAS, WJ UNIV VIRGINIA, USA 33 6.6 0.592 Review The emerging role of transcranial magnetic resonance imaging–guided focused ultrasound in functional neurosurgery
DOBRAKOWSKI PP, 2014, INTERV NEURORADIOL 10.15274/INR-2014-10033 REVIEW INTERV NEURORADIOL 2014 DOBRAKOWSKI, PP MED UNIV SILESIA, POLAND 33 4.12 0.507 Review Movement disorder MR-guided focused ultrasound: a new generation treatment of Parkinson’s disease, essential tremor and neuropathic pain
FISHMAN PS, 2018, MOVEMENT DISORD 10.1002/mds.27401 ARTICLE MOVEMENT DISORD 2018 FISHMAN, PS UNIV MARYLAND SCH MED, USA 32 8 0.489 Human Movement disorder Neurological adverse event profile of magnetic resonance imaging–guided focused ultrasound thalamotomy for essential tremor
MONTEITH SJ, 2013, J NEUROSURG 10.3171/2012.10.JNS12186 ARTICLE J NEUROSURG 2013 MONTEITH, S UNIV VIRGINIA, USA 32 3.56 0.248 Human Pain Transcranial magnetic resonance–guided focused ultrasound surgery for trigeminal neuralgia: a cadaveric and laboratory feasibility study
MOSER D, 2012, NEUROSURG FOCUS 10.3171/2011.10.FOCUS11246 ARTICLE NEUROSURG FOCUS 2012 MOSER, D CTR ULTRASOUND FUNCT NEUROSURG, SWITZERLAND 32 3.2 0.373 Human Targetting error Measurement of targeting accuracy in focused ultrasound functional neurosurgery
JUNG NY, 2019, J NEUROSURG 10.3171/2018.2.JNS172514 ARTICLE J NEUROSURG 2019 CHANG, JW YONSEI UNIV, SOUTH KOREA 31 10.33 0.589 Human Movement disorder The efficacy and limits of magnetic resonance–guided focused ultrasound pallidotomy for Parkinson’s disease: a Phase I clinical trial
WANG F, 2012, PLOS ONE 10.1371/journal.pone.0052925 ARTICLE PLOS ONE 2012 CHEN, Y PEKING UNIV, PEOPLES R CHINA 31 3.1 0.361 Animal Blood-brain barrier Targeted delivery of GDNF through the blood–brain barrier by MRI-guided focused ultrasound
PARK YS, 2019, MOVEMENT DISORD 10.1002/mds.27637 ARTICLE MOVEMENT DISORD 2019 CHANG, JW YONSEI UNIV, SOUTH KOREA 30 10 0.57 Human Movement disorder Four-year follow-up results of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor
APPELBOOM G, 2016, NEURO-ONCOLOGY 10.1093/neuonc/now137 REVIEW NEURO-ONCOLOGY 2016 APPELBOOM, G STANFORD MED CTR, USA 30 5 0.283 Review Stereotactic modulation of blood-brain barrier permeability to enhance drug delivery
KRISHNA V, 2019, NEUROSURGERY 10.1093/neuros/nyy020 ARTICLE NEUROSURGERY 2019 KRISHNA, V OHIO STATE UNIV, USA 29 9.67 0.551 Human Movement disorder Prospective tractography-based targeting for improved safety of focused ultrasound thalamotomy
MENG Y, 2019, ANN NEUROL 10.1002/ana.25604 ARTICLE ANN NEUROL 2019 LIPSMAN, N SUNNYBROOK RES INST, CANADA 28 9.33 0.532 Human Blood-brain barrier Glymphatics visualization after focused ultrasound-induced blood–brain barrier opening in humans

These articles can be divided into three topics depending on the pathology type in which MRgFUS use has been described in the article. Equal numbers of articles involved human studies and animal studies (n = 41). Thirty-six studies were related to blood brain barrier (BBB) disruption and only three studies of these were human studies. Twenty-five studies focused on the role of FUS in patients with movement disorders and all were human studies. Three articles discussed the role of FUS in patients with pain, and a similar number of articles discussed the role of FUS for oncological indications in humans. Eleven articles discussed the technical aspects, while one clinical article described the use of FUS in patients with obsessive-compulsive disorders (OCD).

The article that received the maximum number of citations was “Non-invasive MR Imaging–guided Focal Opening of the Blood-Brain Barrier in Rabbits” published in 2001 in Radiology by Hynynen et al. and cited 855 times (Hynynen et al., 2001). The next two articles in the top 100 list, published in the New England Journal of Medicine, described the clinical application of MRgFUS in essential tremors. The first of these, titled “A Pilot Study of Focused Ultrasound Thalamotomy for Essential Tremor,” was a pilot trial that established the safety and efficacy of focused ultrasound thalamotomy in 15 patients suffering from essential tremor (Elias et al., 2013). Another article published in 2016, titled “A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor,” was a multicentre trial that confirmed the efficacy of focused ultrasound thalamotomy (Elias et al., 2016). The total citations per year for this article were 62.67, the maximum out of 100 cited articles.

 Main information

These 100 articles were published in 45 journals over 22 years (1998–2019). There were 85 original and 15 review articles. The average number of years from the date of publication was 7.22. Interestingly, most of these articles were published recently: 2017 (15 articles), 2018 (12 articles), and 2014 (10 articles) (Figure 1A).

(A) Line graph showing the year wise number of articles published. (B) Line graph showing the year wise average citations per year. (C) Graph showing the number of articles among the top 100 cited articles on MRgFUS published in the different journals. (D) Graphical representation of Bradford’s law.

Average citations per document were 97.78, while average citations per year per document were 12.47 (Table 2). Maximum mean citations per article and mean citations per year were for the articles published in 2001 and were 855 and 42.75, respectively (Figure 1B).

Main information about data.

Description Results
Timespan 1998:2019
Sources (Journals, Books, etc.) 45
Documents 100
Average years from publication 7.22
Average citations per documents 97.78
Average citations per year per doc 12.47
References 2,798
Document types
Article 85
Article; proceedings paper 1
Editorial material 1
Review 13
Document contents
Keywords Plus (ID) 365
Author’s keywords (DE) 169
Authors
Authors 481
Author appearances 833
Authors of single-authored documents 0
Authors of multi-authored documents 481
Authors collaboration
Single-authored documents 0
Documents per Author 0.208
Authors per document 4.81
Co-authors per documents 8.33
Collaboration index 4.81
Journals

Figure 1C shows the top 23 journals that published two or more articles. Journal of Neurosurgery had a maximum of 11 publications, followed by the Journal of Controlled Release (7), Movement Disorders (6 articles), and Neurosurgery (6 articles). Other journals that published at least one of these articles included Stereotactic and Functional Neurosurgery, the Journal of Neurology, Neurosurgery and Psychiatry, and the Journal of Magnetic Resonance Imaging.

Figure 1D shows the graphical representation of Bradford’s Law, which estimates the exponentially diminishing returns of searching for references in science journals. It shows that the Journal of Neurosurgery, Journal of Controlled Release, Movement Disorders, Neurosurgery and Physics in Medicine and Biology lie in Zone 1.

Figure 2A shows the journal-wise distribution of the total citations received by these articles. The articles published in Radiology were cited the most (1,064 citations), followed by New England Journal of Medicine (761 citations) and Journal of Neurosurgery (736 citations). The articles published in these journals were 4, 2, and 11, respectively. Figure 2B shows the journal impact measured in the H-index, with the Journal of Neurosurgery at the top. Figure 2C shows the source dynamics, i.e., the year-wise increase in the number of articles. Journal of Neurosurgery published the first article in 2012, and there has been a rapid increase in the published articles since.

(A) Graph showing the top 20 journals with maximum impact in terms of total citations received by the articles included in the analysis. (B) Graph showing the top 20 journals with maximum impact in terms of H-index of the articles included in the analysis. (C) Line graph showing the “Source growth,” i.e., the cumulative number of articles published in the top seven journals. (D) Graph showing the number of articles among the top 100 cited articles on MRgFUS published by different authors.

 Authors

These top 100 cited articles included 481 authors who made 833 appearances in these 100 articles. The number of co-authors per document was 8.33, with a collaboration index of 4.81. None of these articles were published by a single author.

Figure 2D shows the top 20 authors who published the maximum number of these articles. Hynynen K authored 28 out of these top 100, followed by Elias WJ (15 articles) and Zadicario (12 articles). Supplementary Figure 1 shows the top 20 authors’ production over time, with the size of the dots denoting the number of articles and the shade of the dots denoting the number of citations per year. Figure 3A shows the graphical representation of Lotka’s law, which denotes the distribution of the number of articles published by the number of authors. Most of the authors (85%) published 1 (70%) or 2 (15%) articles. Figure 3B shows the authors whose articles received the maximum number of citations. Articles authored by Hynynen received the maximum number of citations (4130). Table 3 shows the various indexes of the top 50 authors. H-index and g-index were maximum for Hynynen K, while the m-index, which considers the h-index and the number of years an author has been active for, was maximum for Chang JW (1.5710).

(A) Graphical representation of Lotka’s law. (B) Graph showing the top 20 authors with maximum impact as measured by total citations received by the top 100 cited articles on MRgFUS.

Various indexes of the top 50 authors.

Element H Index G Index M Index Total citations Number of articles Production year start
HYNYNEN K 28 28 1.167 4,130 28 1998
ELIAS WJ 15 15 1.5 1,426 15 2012
ZADICARIO E 12 12 0.75 1,460 12 2006
CHANG JW 11 11 1.571 918 11 2015
LIPSMAN N 10 10 1.111 1,298 10 2013
MCDANNOLD N 10 10 0.476 2,318 10 2001
WINTERMARK M 10 10 1 821 10 2012
JOLESZ FA 8 8 0.333 1,853 8 1998
HUANG YX 7 7 0.583 1,012 7 2010
LOZANO AM 7 7 0.778 962 7 2013
VYKHODTSEVA N 7 7 0.333 1,765 7 2001
AUBERT I 6 6 0.5 731 6 2010
CHANG WS 6 6 0.857 394 6 2015
JUNG HH 6 6 0.857 394 6 2015
LIU HL 6 6 0.5 653 6 2010
SHAH BB 6 6 0.667 1,000 6 2013
EAMES M 5 5 0.5 239 5 2012
GHANOUNI P 5 5 0.714 572 5 2015
KASSELL NF 5 5 0.385 252 5 2009
MEDEL R 5 5 0.385 252 5 2009
O’REILLY MA 5 5 0.625 247 5 2014
SCHWARTZ ML 5 5 0.556 493 5 2013
SNELL J 5 5 0.5 239 5 2012
YEH CK 5 5 0.556 371 5 2013
AUBRY JF 4 4 0.333 238 4 2010
FAN CH 4 4 0.444 320 4 2013
GWINN R 4 4 0.667 550 4 2016
HANES J 4 4 0.5 310 4 2014
HUSS DS 4 4 0.5 247 4 2014
KONOFAGOU EE 4 4 0.333 231 4 2010
MENG Y 4 4 1 439 4 2018
MONTEITH SJ 4 4 0.4 494 4 2012
PRICE RJ 4 4 0.5 310 4 2014
SHEEHAN JP 4 4 0.308 196 4 2009
WANG F 4 4 0.308 199 4 2009
WERNER B 4 4 0.308 575 4 2009
ZHANG YZ 4 4 0.364 623 4 2011
BLACK SE 3 3 0.75 310 3 2018
BOCH AL 3 3 0.25 187 3 2010
CHENG Y 3 3 0.231 168 3 2009
DALLAPIAZZA RF 3 3 0.429 523 3 2015
EISENBERG HM 3 3 0.5 463 3 2016
FINK M 3 3 0.25 187 3 2010
FISHMAN PS 3 3 0.5 463 3 2016
HARNOF S 3 3 0.188 206 3 2006
HEYN C 3 3 0.75 411 3 2018
JEANMONOD D 3 3 0.231 513 3 2009
JUNG NY 3 3 0.6 94 3 2017
KLIBANOV AL 3 3 0.375 264 3 2014
KRISHNA V 3 3 0.75 124 3 2018
Affiliations and country

Figure 4A shows the top 20 universities which published the maximum number of articles. The maximum number of authors belong to the University of Toronto. Most universities were from the United States, Canada, Israel, and Taiwan.

(A) Bar graph showing the top 20 affiliations of the authors who authored these top 100 cited articles. (B) Bar graph showing the countries which published the top 100 cited articles. Orange indicates publications with authors from more than one country (i.e., multicountry collaboration).

These top 100 cited articles were authored by corresponding authors from 11 countries, showing the limited availability of this technology. Figure 4B shows the country-wise distribution of the corresponding authors of these top 100 cited articles, with the maximum number of articles (n = 45) published from the United States. It was followed by Canada (19 articles) and China (10 articles). There were significant international collaborations in these articles, as shown by the orange bars in Figure 4B. The MCP ratio (Multicountry production ratio, which is the ratio of articles authored by authors belonging to more than one country to those authored by authors from one single country) was maximum (= 1) for the articles published by the authors from Switzerland and Finland, suggesting that all their articles had multicountry collaborations. Even the articles published from the United States had an MCP ratio of 0.31, with 14 out of 45 articles having authors from countries other than the United States. Figure 5A shows the world map with different shades of blue, showing the countries of all the authors (not corresponding authors alone) who were part of the author list of these 100 articles. It shows that most of the authors belonged to North America and Europe. Figure 5B shows the number of times the articles from a given country (as per the corresponding author) were cited. The articles from the United States were cited 5,125 times, followed by Canada (1,814 citations) and China (852 citations). However, average citations per article were maximum for the articles published from Switzerland (142), followed by the articles from the United States (113.9).

(A) Shade graded world map showing the distribution of scientific publications per the total number of authors from a country with the darker shade implying a greater number of authors from a country. (B) Graph showing the number of citations received by the articles published from various countries (as per the country of the corresponding author).

Figure 6A shows the number of times the top 20 cited articles were cited in all the journals, with the article by Hynynen et al. published in Radiology in 2011 cited 855 times. Figure 6B shows the number of times these top 100 cited articles were cited in these top 100 cited articles. Article by Hynynen et al. published in Radiology in 2011 was cited in 40 out of these top 100 cited articles.

(A) Graph showing the number of times the top 20 cited articles were cited in all the journals. (B) Graph showing the number of times these top 100 cited articles were cited in these top 100 cited articles.

Supplementary Figure 2 shows the most commonly used keywords in these top 100 cited articles. The most common keyword was “focused ultrasound,” followed by “blood-brain barrier” and “essential tremor.”

Supplementary Figure 3 shows the three-field plot between the author country (left field), author (center field), and the keywords (right field). It can be appreciated that the countries with a maximum number of connections were Canada and the United States of America (USA). In contrast, the authors with the maximum number of connections were Hynynen K, Lozano AM, Lipsman N, and Elias WJ.

 Discussion

MRgFUS is one of the most evolving field in the neurosurgery This scientometric analysis of the MRgFUS revealed some interesting and intriguing trends. First, these articles were published over the last 22 years, from 1998 to 2019. Obviously, it takes a few years for any article to garner many citations to feature in the top 100 cited articles and more importantly adoption in the clinical field given novelty of the technology. However, articles published recently, as recent as in 2019, appeared in this top 100 list. This reflects the rapid evolution and the acceptance of the field, not only by clinician but also the patients. As this technology is evolving and explored in newer neuropsychiatric indications, the scientific publications and their citations are going to be more voluminous and robust in near future.

Secondly, only 11 countries contributed to these top 100 cited articles, with the top 2 countries (the United States and Canada) contributing to more than half of these articles. As MRgFUS is a new technology and its availability is yet limited. There was no article from low to middle-income countries, perhaps due to the high cost of initial set up. The low acceptance of a surgical procedure for non-life-threatening diseases may also contribute to the limited interest of many countries. Although the average citations per document of these articles were less when compared with the top 100 cited articles on other pathologies, the average citations per document per year were higher (Agrawal et al., 2021). This reflects not only that most of these articles were published recently but also that they are being increasingly cited and applied increasingly to clinical and translational research.

The analysis revealed that 41 articles were based on animal or cadaveric studies to study the preclinical aspects of focused ultrasound. It again reflects the novelty of the technology and value of translational impact in clinical neurosurgery. Amongst the human studies, most of the articles (n = 25) described the use of MRgFUS in various movement disorders, with essential tremor being the commonest pathology. The other rare pathologies where the use of MRgFUS has been described in these studies are Parkinson’s disease, dystonia, and OCD.

There was one animal study and four human trials in the top five cited articles (Hynynen et al., 2001; McDannold et al., 2010; Elias et al., 2013, 2016; Lipsman et al., 2014). The highest cited article was an animal study. Hynynen et al. studied if focused ultrasound beams can be used to locally open the blood-brain barrier without damage to surrounding brain tissue and if magnetic resonance (MR) imaging can be used to monitor this procedure in this article (Hynynen et al., 2001). The authors established that the BBB could be consistently opened with transcranial FUS, opening a new translational field in neurological disorders.

Three out of four human trials were proof of concept studies or pilot studies (McDannold et al., 2010; Elias et al., 2013, 2016). The second most cited article was a pilot study by Elias et al. and published in NEJM in 2013 (Elias et al., 2013). The authors reported total tremor and disability scores improved from 54.9 to 24.3 (P = 0.001) and 18.2 to 2.8 (P = 0.001), respectively in 15 ET patients treated with FUS thalamotomy. This pilot trial was followed by a multicentric randomized controlled trial, published in NEJM in 2016, comparing the efficacy of unilateral focused ultrasound thalamotomy with a sham procedure in 76 patients with ET (Elias et al., 2016). The authors observed that hand-tremor scores improved more after focused ultrasound thalamotomy than after sham procedure, and the improvement was maintained 12 months after thalamotomy. Improvement in secondary outcome measures assessing disability and quality of life was also noticed.

These 100 top cited articles were published in in 45 various neurosurgical, neurological, radiological, and basic sciences research journals, including high-impact journals like NEJM, JAMA Neurology, Nature communications, Annals of Neurology, Movement Disorders, Radiology, and Neurosurgery. This diversity may represent the interest from different specialties, leading to faster advancements in this technology and a steep increase in the amount of literature. Journal of Neurosurgery published 11 out of these top 100, perhaps related to the fact that neurosurgeons are the end users of this technology and have been actively involved in FUS-related research.

The top-cited article by Hynynen guided Radiology to be the maximally cited journal out of all the journals in which these articles were published (Hynynen et al., 2001).

One of the important finding noted in this study was that the number of co-authors per document was 8.33, indicating that these articles were published by research teams with larger collaborative members and/or multicentric collaboration. Moreover, 15% of the authors contributed to more than two articles in the top 100 cited articles. Hynynen K, a Professor of Medical Biophysics at the University of Toronto, was the top contributor in these journals, contributing to 28 out of these top 100 cited articles, followed by Elias WJ (15 articles) and Zadicario (12 articles). The second highest contributor to these articles is Elias WJ, a Professor of Neurological Surgery at the University of Virginia. The third highest contributor was Eyal Zadicario, who is a part of the InSightec (manufacturer) team. Hynynen K has contributed to FUS research for more than three decades and is the lead author of the highly cited article in this list.

Limitations

There are some inherent drawbacks of bibliometric analysis. The reasons why a paper is cited multiple times may be diverse and may not accurately reflect the influence of the study in question (Garfield, 1979). Sole reliance on these indicators can lead to missing specific papers reporting (Allen et al., 2009). Similarly, recent publications on the topic and young researchers might not have accrued enough citations to make it to the list of top 100 articles. One of the inherent limitation of this study is that the search criteria included both the animal and human studies. It is not uncommon to have lesser citation of the animal studies than human studies, given recent and increasingly more acceptance in clinical trials and clinical practise. The citation matrix alone should not be taken as the sole criteria about the value and rigor of the study. The search was conducted on Web of Science, the most common database used for bibliometric analyses, but still, fallacious exclusions of some articles could have happened due to the keyword-specific results obtained.

 Conclusion

MRgFUS is one of the fastest evolving field in neurosurgery, specifically functional neurosurgery with increasing studies in recent years. As novel indications are studied, it is crucial to identify the most important topics and contributors to the field as scientific literature expands to guide clinician and research in the field. Most of the top 100 cited articles comes from North America and Europe, with the United States and Canada contributing to more than half of the articles on MRgFUS. The top 100 cited articles also highlight the access of MRgFUS to developed countries and healthcare disparity in access of MrgFUS to developing countries.

 Author contributions

KG: conceptualization, methodology, software, writing, rewriting and editing, data curation, writing—original draft preparation, visualization, investigation, software, and validation. MR: conceptualization, writing, rewriting and editing, writing—original draft preparation, visualization, investigation, supervision, software, and validation. VK: conceptualization, methodology, rewriting and editing, and supervision. MS and AR: methodology, rewriting and editing, and supervision. All authors contributed to the article and approved the submitted version.

 Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

 Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

 Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnhum.2022.981571/full#supplementary-material

Graph showing the year wise distribution of number of articles among the top 100 cited articles on MRgFUS published by different authors and the number of citations received by articles published in different years.

Graph showing most frequently used keywords in the top 100 cited articles on MRgFUS.

Three fields plot showing the predominant countries, surgeons and the key areas of work from the top 100 cited articles on MRgFUS.

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