Publications

@article{pmid42822751,

title = {Ultrasound technologies to assess bone health: Past, present and future},

author = {Kay Raum and Keith Wear and Quentin Grimal and Mami Matsukawa and Kfir Lapid and Edgar Wiebe and Jean-Gabriel Minonzio},

doi = {10.1016/j.bone.2026.118120},

issn = {1873-2763},

year  = {2027},

date = {2027-01-01},

journal = {Bone},

volume = {214},

pages = {118120},

abstract = {BACKGROUND: Dual-energy X-ray absorptiometry (DXA) is currently the clinical reference standard for osteoporosis diagnosis and fracture risk assessment. However, it provides only a partial description of bone strength and has practical limitations related to accessibility and ionizing radiation. Over the past three decades, quantitative ultrasound (QUS) technologies have evolved from empirical heel-based measurements to advanced imaging approaches capable of characterizing cortical bone structure and material properties.nnOBJECTIVES: To review the development of bone ultrasound technologies, summarize their clinical evidence for fracture risk assessment, and discuss the opportunities and challenges of emerging ultrasound-based approaches.nnFINDINGS: First-generation calcaneal QUS devices demonstrate fracture prediction comparable to peripheral DXA in large prospective studies and remain valuable for fracture risk assessment, particularly where DXA is unavailable or repeated X-ray examinations are undesirable. Their broader clinical adoption was limited mainly by device-specific algorithms, lack of standardization, and the absence of universally accepted diagnostic thresholds. Newer ultrasound technologies extend assessment to clinically relevant skeletal sites, including the hip and spine, or directly quantify cortical bone structure and material properties at peripheral sites. Radiofrequency echographic multi-spectrometry (REMS) has shown encouraging results in cross-sectional and prospective studies but relies on proprietary reference models and algorithms that require greater transparency and independent validation. Second-generation technologies, including cortical backscatter analysis (CortBS) and refraction-corrected imaging, provide quantitative measurements of cortical thickness, porosity-related microstructure, wave speed, attenuation and other biomechanical biomarkers in physical SI units, enabling independent validation and multiparametric fracture-risk modeling. However, until now these technologies have only been validated ex-vivo on human cadaver bones and in-vivo in small exploratory cross-sectional fracture discrimination studies. Multicenter cross-sectional and prospective studies are underway to create reference data and to establish their value for fracture risk prediction.nnCONCLUSIONS: Bone ultrasound has progressed from an empirical screening tool to a family of quantitative technologies capable of assessing complementary aspects of bone quality and quantity. Calcaneal QUS is currently the only technology with an established guideline-recognized role in fracture risk assessment. Prospective multicenter fracture risk prediction studies, as well as technical standardization and transparent validation studies showing cross-vendor reproducibility and independent replication are now required to define the clinical role of newer ultrasound technologies and support their integration into future osteoporosis management and clinical routine use.},

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}

@article{nokey,

title = {The respective and dependent effects of scattering and bone matrix absorption on ultrasound attenuation in cortical bone},

author = {Brett Austin McCandless and Kay Raum and Marie Muller },

doi = {10.1088/1361-6560/ad3fff},

year  = {2024},

date = {2024-05-20},

journal = {Physics in Medicine & Biology},

volume = {69},

number = {11},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tang2024,

title = {Study on Synergistic Effects of Nanohydroxyapatite/High-Viscosity Carboxymethyl Cellulose Scaffolds Stimulated by LIPUS for Bone Defect Repair of Rats},

author = {Liang Tang and Tianpei Wu and Jiaxiang Li and Yanan Yu and Zhanke Ma and Lijun Sun and Dean Ta and Xiushan Fan},

doi = {10.1021/acsbiomaterials.3c01381},

issn = {2373-9878},

year  = {2024},

date = {2024-02-12},

journal = {ACS Biomater. Sci. Eng.},

volume = {10},

number = {2},

pages = {1018--1030},

publisher = {American Chemical Society (ACS)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Renaud2023,

title = {Current Challenges in Ultrasound Imaging of Cortical Bone Thickness},

author = {Guillaume Renaud and Jean-Gabriel Minonzio},

doi = {10.1016/j.acra.2023.08.043},

issn = {1076-6332},

year  = {2023},

date = {2023-12-00},

journal = {Academic Radiology},

volume = {30},

number = {12},

pages = {3162--3164},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nguyen2023,

title = {Measuring the alveolar bone level in adolescents: A comparison between ultrasound and cone beam computed tomography},

author = {Kim‐Cuong T. Nguyen and Lawrence H. Le and Neelambar R. Kaipatur and Fabiana T. Almeida and Hollis Lai and Edmond H. M. Lou and Paul W. Major},

doi = {10.1111/ipd.13092},

issn = {1365-263X},

year  = {2023},

date = {2023-09-00},

journal = {Int J Paed Dentistry},

volume = {33},

number = {5},

pages = {487--497},

publisher = {Wiley},

abstract = {AbstractBackgroundCone beam computed tomography (CBCT) is an imaging modality, which is used routinely in orthodontic diagnosis and treatment planning but delivers much higher radiation than conventional dental radiographs. Ultrasound is a noninvasive imaging method that creates an image without ionizing radiation.AimTo investigate the reliability of ultrasound and the agreement between ultrasound and CBCT in measuring the alveolar bone level (ABL) on the buccal/labial side of the incisors in adolescent orthodontic patients.DesignOne hundred and eighteen incisors from 30 orthodontic adolescent patients were scanned by CBCT with 0.3‐mm voxel size and ultrasound at 20 MHz frequency. The ABL, distance from the cementoenamel junction (CEJ) to the alveolar bone crest (ABC), was measured twice to evaluate the agreement between ultrasound and CBCT. In addition, the intra‐ and inter‐rater reliabilities in measuring the ABL by four raters were compared.ResultsThe mean difference (MD) in the ABL between ultrasound and CBCT was −0.07 mm with 95% limit of agreement (LoA) from −0.47 to 0.32 mm for all teeth. For each jaw, the MDs between the ultrasound and CBCT were −0.18 mm (for mandible with 95% LoA from −0.53 to 0.18 mm) and 0.03 mm (for maxilla with 95% LoA from −0.28 to 0.35 mm). In comparison, ultrasound had higher intra‐rater (ICC = 0.83–0.90) and inter‐rater reliabilities (ICC = 0.97) in ABL measurement than CBCT (ICC = 0.56–0.78 for intra‐rater and ICC = 0.69 for inter‐rater reliabilities).ConclusionCBCT parameters used in orthodontic diagnosis and treatment planning in adolescents may not be a reliable tool to assess the ABL for the mandibular incisors. On the contrary, ultrasound imaging, an ionizing radiation‐free, inexpensive, and portable diagnostic tool, has potential to be a reliable diagnostic tool in assessing the ABL in adolescent patients.},

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pubstate = {published},

tppubtype = {article}

}

@article{Tang2023,

title = {Low-intensity pulsed ultrasound enhances the positive effects of high-intensity treadmill exercise on bone in rats},

author = {Liang Tang and Hao Guo and Keyi Wang and Yaling Zhou and Tianpei Wu and Xiushan Fan and Jianzhong Guo and Lijun Sun and Dean Ta},

doi = {10.1007/s00774-023-01439-6},

issn = {1435-5604},

year  = {2023},

date = {2023-09-00},

journal = {J Bone Miner Metab},

volume = {41},

number = {5},

pages = {592--605},

publisher = {Springer Science and Business Media LLC},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Karbalaeisadegh2023,

title = {Ultrasound Characterization of Cortical Bone Using Shannon Entropy},

author = {Yasamin Karbalaeisadegh and Shanshan Yao and Yong Zhu and Quentin Grimal and Marie Muller},

doi = {10.1016/j.ultrasmedbio.2023.04.006},

issn = {0301-5629},

year  = {2023},

date = {2023-08-00},

journal = {Ultrasound in Medicine & Biology},

volume = {49},

number = {8},

pages = {1824--1829},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Puts2023,

title = {Focused Low-Intensity Pulsed Ultrasound (FLIPUS) Mitigates Apoptosis of MLO-Y4 Osteocyte-like Cells},

author = {Regina Puts and Aseel Khaffaf and Maria Shaka and Hui Zhang and Kay Raum},

doi = {10.3390/bioengineering10030387},

issn = {2306-5354},

year  = {2023},

date = {2023-03-00},

journal = {Bioengineering},

volume = {10},

number = {3},

publisher = {MDPI AG},

abstract = {Long cytoplasmic processes of osteocytes orchestrate bone activity by integration of biochemical and mechanical signals and regulate load-induced bone adaptation. Low-Intensity Pulsed Ultrasound (LIPUS) is a clinically used technique for fracture healing that delivers mechanical impulses to the damaged bone tissue in a non-invasive and non-ionizing manner. The mechanism of action of LIPUS is still controversially discussed in the scientific community. In this study, the effect of focused LIPUS (FLIPUS) on the survival of starved MLO-Y4 osteocytes was investigated in vitro. Osteocytes stimulated for 10 min with FLIPUS exhibited extended dendrites, which formed frequent connections to neighboring cells and spanned longer distances. The sonicated cells displayed thick actin bundles and experienced increase in expression of connexin 43 (Cx43) proteins, especially on their dendrites, and E11 glycoprotein, which is responsible for the elongation of cellular cytoplasmic processes. After stimulation, expression of cell growth and survival genes as well as genes related to cell–cell communication was augmented. In addition, cell viability was improved after the sonication, and a decrease in ATP release in the medium was observed. In summary, FLIPUS mitigated apoptosis of starved osteocytes, which is likely related to the formation of the extensive dendritic network that ensured cell survival.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gaujac2023,

title = {Does the bone mineral density measured on a preoperative CT scan before total hip arthroplasty reflect the bone's mechanical properties?},

author = {Nicolas Gaujac and Elhadi Sariali and Quentin Grimal},

doi = {10.1016/j.otsr.2022.103348},

issn = {1877-0568},

year  = {2023},

date = {2023-02-00},

journal = {Orthopaedics & Traumatology: Surgery & Research},

volume = {109},

number = {1},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dia2023,

title = {The influence of intra-cortical microstructure on the contrast in ultrasound images of the cortex of long bones: A 2D simulation study},

author = {Amadou Sall Dia and Guillaume Renaud and Aida Hejazi Nooghabi and Quentin Grimal},

doi = {10.1016/j.ultras.2022.106831},

issn = {0041-624X},

year  = {2023},

date = {2023-01-00},

journal = {Ultrasonics},

volume = {127},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Feng2023,

title = {Nakagami statistics-based photoacoustic spectroscopy used for label-free assessment of bone tissue},

author = {Ting Feng and Yihan Zhu and Xiaoxiang Gao and Weiya Xie and Haigang Ma and Liming Cheng and Dean Ta and Qian Chen},

doi = {10.1364/ol.477011},

issn = {1539-4794},

year  = {2023},

date = {2023-00-00},

journal = {Opt. Lett.},

volume = {48},

number = {3},

publisher = {Optica Publishing Group},

abstract = {Quick identification of abnormal molecular metabolism of bone tissues is challenging. Photoacoustic (PA) spectroscopy techniques have great potential in molecular imaging. However, most of them are amplitude-dependent and easily affected by the light deposition, especially for bone tissues with high optical scattering. In this Letter, we propose a Nakagami statistics-based PA spectroscopy (NSPS) method for characterizing molecules in bone tissues. We indicate that the NSPS curve can intelligently identify changes in the content of molecules in bone tissues, with a high disturbance-resisting ability. The NSPS has remarkable potential for use in the early and rapid detection of bone diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Minonzio2022,

title = {Bi-Directional Axial Transmission measurements applied in a clinical environment},

author = {Jean-Gabriel Minonzio and Donatien Ramiandrisoa and Johannes Schneider and Eva Kohut and Melanie Streichhahn and Ulrik Stervbo and Rainer Wirth and Timm Henning Westhoff and Kay Raum and Nina Babel},

editor = {John Leicester Williams},

doi = {10.1371/journal.pone.0277831},

issn = {1932-6203},

year  = {2022},

date = {2022-12-30},

journal = {PLoS ONE},

volume = {17},

number = {12},

publisher = {Public Library of Science (PLoS)},

abstract = {Accurate measurement of cortical bone parameters may improve fracture risk assessment and help clinicians on the best treatment strategy. Patients at risk of fracture are currently detected using the current X-Ray gold standard DXA (Dual XRay Absorptiometry). Different alternatives, such as 3D X-Rays, Magnetic Resonance Imaging or Quantitative Ultrasound (QUS) devices, have been proposed, the latter having advantages of being portable and sensitive to mechanical and geometrical properties. The objective of this cross-sectional study was to evaluate the performance of a Bi-Directional Axial Transmission (BDAT) device used by trained operators in a clinical environment with older subjects. The device, positioned at one-third distal radius, provides two velocities: VFAS (first arriving signal) and VA0 (first anti-symmetrical guided mode). Moreover, two parameters are obtained from an inverse approach: Ct.Th (cortical thickness) and Ct.Po (cortical porosity), along with their ratio Ct.Po/Ct.Th. The areal bone mineral density (aBMD) was obtained using DXA at the femur and spine. One hundred and six patients (81 women, 25 men) from Marien Hospital and St. Anna Hospital (Herne, Germany) were included in this study. Age ranged from 41 to 95 years, while body mass index (BMI) ranged from 16 to 47 kg.m−2. Three groups were considered: 79 non-fractured patients (NF, 75±13years), 27 with non-traumatic fractures (F, 80±9years) including 14 patients with non-vertebral fractures (NVF, 84±7years). Weak to moderate significant Spearman correlations (Rranging from 0.23 to 0.53,p< 0.05) were found between ultrasound parameters and age, BMI. Using multivariate Partial Least Square discrimination analyses with Leave-One-Out Cross-Validation (PLS-LOOCV), we found the combination of VFAS and the ratio Ct.Po/Ct.Th to be predictive for all non traumatic fractures (F) with the odds ratio (OR) equals to 2.5 [1.6-3.4] and the area under the ROC curve (AUC) equal to 0.63 [0.62-0.65]. For the group NVF, combination of four parameters VA0. Ct.Th, Ct.Po and Ct.Po/Ct.Po, along with age provides a discrimination model with OR and AUC equals to 7.5 [6.0-9.1] and 0.75 [0.73-0.76]. When restricted to a smaller population (87 patients) common to both BDAT and DXA, BDAT ORs and AUCs are comparable or slightly higher to values obtained with DXA. The fracture risk assessment by BDAT method in older patients, in a clinical setting, suggests the benefit of the affordable and transportable device for the routine use.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cordova2022,

title = {HER2 classification in breast cancer cells: A new explainable machine learning application for immunohistochemistry},

author = {Claudio Cordova and Roberto Muñoz and Rodrigo Olivares and Jean-Gabriel Minonzio and Carlo Lozano and Paulina Gonzalez and Ivanny Marchant and Wilfredo González‑Arriagada and Pablo Olivero},

doi = {10.3892/ol.2022.13630},

issn = {1792-1082},

year  = {2022},

date = {2022-12-14},

journal = {Oncol Lett},

volume = {25},

number = {2},

publisher = {Spandidos Publications},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Behforootan2022,

title = {Can guided wave ultrasound predict bone mechanical properties at the femoral neck in patients undergoing hip arthroplasty?},

author = {Sara Behforootan and Madelaine Thorniley and Jean-Gabriel Minonzio and Oliver Boughton and Monil Karia and Rajarshi Bhattacharya and Ulrich Hansen and Justin Cobb and Richard Abel},

doi = {10.1016/j.jmbbm.2022.105468},

issn = {1751-6161},

year  = {2022},

date = {2022-12-00},

journal = {Journal of the Mechanical Behavior of Biomedical Materials},

volume = {136},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chen2022,

title = {Influence of optical transmissivity on signal characteristics of photoacoustic guided waves in long cortical bone},

author = {Honglei Chen and Kailiang Xu and Xiaoyu Liu and Ying Li and Zenghua Liu and Dean Ta},

doi = {10.1016/j.ultras.2022.106816},

issn = {0041-624X},

year  = {2022},

date = {2022-12-00},

journal = {Ultrasonics},

volume = {126},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zhang2022,

title = {A Tissue Engineering Acoustophoretic (TEA) Set-up for the Enhanced Osteogenic Differentiation of Murine Mesenchymal Stromal Cells (mMSCs)},

author = {Hui Zhang and Nirina Beilfuss and Urszula Zabarylo and Kay Raum and Regina Puts},

doi = {10.3390/ijms231911473},

issn = {1422-0067},

year  = {2022},

date = {2022-10-00},

journal = {IJMS},

volume = {23},

number = {19},

publisher = {MDPI AG},

abstract = {Quickly developing precision medicine and patient-oriented treatment strategies urgently require novel technological solutions. The randomly cell-populated scaffolds usually used for tissue engineering often fail to mimic the highly anisotropic characteristics of native tissue. In this work, an ultrasound standing-wave-based tissue engineering acoustophoretic (TEA) set-up was developed to organize murine mesenchymal stromal cells (mMSCs) in an in situ polymerizing 3-D fibrin hydrogel. The resultant constructs, consisting of 17 cell layers spaced at 300 µm, were obtained by continuous wave ultrasound applied at a 2.5 MHz frequency. The patterned mMSCs preserved the structured behavior within 10 days of culturing in osteogenic conditions. Cell viability was moderately increased 1 day after the patterning; it subdued and evened out, with the cells randomly encapsulated in hydrogels, within 21 days of culturing. Cells in the structured hydrogels exhibited enhanced expression of certain osteogenic markers, i.e., Runt-related transcription factor 2 (RUNX2), osterix (Osx) transcription factor, collagen-1 alpha1 (COL1A1), osteopontin (OPN), osteocalcin (OCN), and osteonectin (ON), as well as of certain cell-cycle-progression-associated genes, i.e., Cyclin D1, cysteine-rich angiogenic inducer 61 (CYR61), and anillin (ANLN), when cultured with osteogenic supplements and, for ANLN, also in the expansion media. Additionally, OPN expression was also augmented on day 5 in the patterned gels cultured without the osteoinductive media, suggesting the pro-osteogenic influence of the patterned cell organization. The TEA set-up proposes a novel method for non-invasively organizing cells in a 3-D environment, potentially enhancing the regenerative properties of the designed anisotropic constructs for bone healing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tran2022b,

title = {Ultrasonic Guided Waves in Bone: A Decade of Advancement in Review},

author = {Tho N. H. T. Tran and Lawrence H. Le and Dean Ta},

doi = {10.1109/tuffc.2022.3197095},

issn = {1525-8955},

year  = {2022},

date = {2022-10-00},

journal = {IEEE Trans. Ultrason., Ferroelect., Freq. Contr.},

volume = {69},

number = {10},

pages = {2875--2895},

publisher = {Institute of Electrical and Electronics Engineers (IEEE)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Miranda2022,

title = {Improvement of Patient Classification Using Feature Selection Applied to Bidirectional Axial Transmission},

author = {Diego Miranda and Rodrigo Olivares and Roberto Munoz and Jean-Gabriel Minonzio},

doi = {10.1109/tuffc.2022.3195477},

issn = {1525-8955},

year  = {2022},

date = {2022-09-00},

journal = {IEEE Trans. Ultrason., Ferroelect., Freq. Contr.},

volume = {69},

number = {9},

pages = {2663--2671},

publisher = {Institute of Electrical and Electronics Engineers (IEEE)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pham2022,

title = {Investigation of ultrasonic soft tissue-bone reflection coefficients correlating with curve severity in children with adolescent idiopathic scoliosis},

author = {Thanh-Tu Pham and Lawrence H Le and Mahdieh Khodaei and Rui Zheng and Edmond Lou},

doi = {10.1177/09544119221114200},

issn = {2041-3033},

year  = {2022},

date = {2022-09-00},

journal = {Proc Inst Mech Eng H},

volume = {236},

number = {9},

pages = {1403--1413},

publisher = {SAGE Publications},

abstract = { Adolescent idiopathic scoliosis (AIS) is a three-dimensional curvature of spine. Children with AIS and low bone quality have higher chance to get curve progression leading to bigger spinal curvature. In addition, bone quality affects acoustic impedance of bone, thus influencing the reflection coefficient of ultrasound signal from the soft tissue–bone interface. This study aimed to estimate the bone quality of AIS patients based on the reflection coefficients to determine the correlation of the bone quality with curve severity. A simple bone model was used to develop an equation to calculate the reflection coefficient value. Experiments were conducted on five different phantoms. Acrylic was used to design a vertebral shape to study the effect of surface roughness and inclination, including: smooth flat surface (SFS), smooth curved surface (SCS), rough curved surface (RCS), and the rough curved inclined surface (RCIS). A clinical study with 37 AIS patients were recruited. The estimated reflection coefficient values of plate phantoms agreed well with the predicted values and the maximum error was 6.7%. The reflection coefficients measured from the acrylic-water interface for the SFS, SCS, RCS, RCIS (3° and 5°) were 0.37, 0.33, 0.28, (0.23 and 0.12), respectively. The surface roughness and inclination increased the reflection loss. From the clinical data, the average reflection coefficients for children with AIS were 0.11 and 0.07 for the mild curve group and the moderate curve group, respectively. A moderate linear correlation was found between the reflection coefficients and curve severity ([Formula: see text] = 0.3). Patients with lower bone quality have observed to have larger spinal curvature. },

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pubstate = {published},

tppubtype = {article}

}