Recently, ultrasound transit time spectroscopy (UTTS) was proposed as a promising method for bone quantitative ultrasound measurement. Studies have showed that UTTS could estimate the bone volume fraction and other trabecular bone structure in ultrasonic through-transmission measurements. The goal of this study was to explore the feasibility of UTTS to be adapted in ultrasonic backscatter measurement and further evaluate the performance of backscattered ultrasound transit time spectrum (BS-UTTS) in the measurement of cancellous bone density and structure. First, taking ultrasonic attenuation into account, the concept of BS-UTTS was verified on ultrasonic backscatter signals simulated from a set of scatterers with different positions and intensities. Then, in vitro backscatter measurements were performed on 26 bovine cancellous bone specimens. After a logarithmic compression of the BS-UTTS, a linear fitting of the log-compressed BS-UTTS versus ultrasonic propagated distance was performed and the slope and intercept of the fitted line for BS-UTTS were determined. The associations between BS-UTTS parameters and cancellous bone features were analyzed using simple linear regression. The results showed that the BS-UTTS could make an accurate deconvolution of the backscatter signal and predict the position and intensity of the simulated scatterers eliminating phase interference, even the simulated backscatter signal was with a relatively low signal-to-noise ratio. With varied positions and intensities of the scatterers, the slope of the fitted line for the log-compressed BS-UTTS versus ultrasonic propagated distance (i.e., slope of BS-UTTS for short) yield a high agreement (r2 = 99.84%–99.96%) with ultrasonic attenuation in simulated backscatter signal. Compared with the high-density cancellous bone, the low-density specimen showed more abundant backscatter impulse response in the BS-UTTS. The slope of BS-UTTS yield a significant correlation with bone mineral density (r = 0.87; p < 0.001), BV/TV (r = 0.87; p < 0.001), and cancellous bone microstructures (r up to 0.87; p < 0.05). The intercept of BS-UTTS was also significantly correlated with bone densities (r = –0.87; p < 0.001) and trabecular structures (|r|=0.43–0.80; p < 0.05). However, the slope of the BS-UTTS underestimated attenuation when measurements were performed experimentally. In addition, a significant non-linear relationship was observed between the measured attenuation and the attenuation estimated by the slope of the BS-UTTS. This study demonstrated that the UTTS method could be adapted to ultrasonic backscatter measurement of cancellous bone. The derived slope and intercept of BS-UTTS could be used in the measurement of bone density and microstructure. The backscattered ultrasound transit time spectroscopy might have potential in the diagnosis of osteoporosis in the clinic.

1.
T. D.
Rachner
,
S.
Khosla
, and
L. C.
Hofbauer
, “
Osteoporosis: Now and the future
,”
Lancet
377
(
9773
),
1276
1287
(
2011
).
2.
P.
Andreopoulou
and
R. S.
Bockman
, “
Management of postmenopausal osteoporosis
,”
Annu. Rev. Med.
66
,
329
342
(
2015
).
3.
P.
Pisani
,
M. D.
Renna
,
F.
Conversano
,
E.
Casciaro
,
M.
Di Paola
,
E.
Quarta
, and
S.
Casciaro
, “
Major osteoporotic fragility fractures: Risk factor updates and societal impact
,”
World J. Orthop.
7
(
3
),
171
181
(
2016
).
4.
R.
Lorente-Ramos
,
J.
Azpeitia-Armán
,
A.
Muñoz-Hernández
,
J. M.
García-Gómez
,
P.
Díez-Martínez
, and
M.
Grande-Bárez
, “
Dual-energy x-ray absorptiometry in the diagnosis of osteoporosis: A practical guide
,”
AJR-Am. J. Roentgenol.
196
(
4
),
897
904
(
2011
).
5.
C.-C.
Glüer
,
M.
Jergas
, and
D.
Hans
, “
Peripheral measurement techniques for the assessment of osteoporosis
,”
Semin. Nucl. Med.
27
(
3
),
229
247
(
1997
).
6.
T. M.
Link
,
S.
Majumdar
,
P.
Augat
,
J. C.
Lin
,
D.
Newitt
,
Y.
Lu
,
N. E.
Lane
, and
H. K.
Genant
, “
In vivo high resolution MRI of the calcaneus: Differences in trabecular structure in osteoporosis patients
,”
J. Bone Miner. Res.
13
(
7
),
1175
1182
(
1998
).
7.
R.
Krug
,
A. J.
Burghardt
,
S.
Majumdar
, and
T. M.
Link
, “
High-resolution imaging techniques for the assessment of osteoporosis
,”
Radiologic Clinics
48
(
3
),
601
621
(
2010
).
8.
G. J.
Kazakia
,
B.
Hyun
,
A. J.
Burghardt
,
R.
Krug
,
D. C.
Newitt
,
A. E.
de Papp
, and
S.
Majumdar
, “
In vivo determination of bone structure in postmenopausal women: A comparison of HR‐pQCT and high‐field MR imaging
,”
J. Bone Miner. Res.
23
(
4
),
463
474
(
2008
).
9.
P.
Laugier
and
G.
Haïat
,
Bone Quantitative Ultrasound
(
Springer
,
Dordrecht
,
2011
), Vol. 576.
10.
K. A.
Wear
,
S.
Nagaraja
,
M. L.
Dreher
, and
S. L.
Gibson
, “
Relationships of quantitative ultrasound parameters with cancellous bone microstructure in human calcaneus in vitro
,”
J. Acoust. Soc. Am.
131
(
2
),
1605
1612
(
2012
).
11.
Z.
Liu
,
L.
Song
,
L.
Bai
,
K.
Xu
, and
D.
Ta
, “
Vibro-acoustic stimulating ultrasonic guided waves in long bone
,”
Acta Physica Sinica
66
(
15
),
154303
(
2017
).
12.
M. A.
Hakulinen
,
J. S.
Day
,
J.
Töyräs
,
M.
Timonen
,
H.
Kröger
,
H.
Weinans
,
I.
Kiviranta
, and
J. S.
Jurvelin
, “
Prediction of density and mechanical properties of human trabecular bone in vitro by using ultrasound transmission and backscattering measurements at 0.2–6.7 MHz frequency range
,”
Phys. Med. Biol.
50
(
8
),
1629
1642
(
2005
).
13.
L.
Lin
,
J.
Cheng
,
W.
Lin
, and
Y.-X.
Qin
, “
Prediction of trabecular bone principal structural orientation using quantitative ultrasound scanning
,”
J. Biomech.
45
(
10
),
1790
1795
(
2012
).
14.
N.
Bochud
,
Q.
Vallet
,
J.-G.
Minonzio
, and
P.
Laugier
, “
Predicting bone strength with ultrasonic guided waves
,”
Sci. Rep.
7
(
1
),
43628
(
2017
).
15.
C. C.
Glüer
,
R.
Eastell
,
D. M.
Reid
,
D.
Felsenberg
,
C.
Roux
,
R.
Barkmann
, and
S.
Kolta
, “
Association of five quantitative ultrasound devices and bone densitometry with osteoporotic vertebral fractures in a population‐based sample: The OPUS Study
,”
J. Bone Min, Res.
19
(
5
),
782
793
(
2004
).
16.
F.
Padilla
,
F.
Jenson
,
V.
Bousson
,
F.
Peyrin
, and
P.
Laugier
, “
Relationships of trabecular bone structure with quantitative ultrasound parameters: In vitro study on human proximal femur using transmission and backscatter measurements
,”
Bone
42
(
6
),
1193
1202
(
2008
).
17.
K. A.
Wear
,
S.
Nagaraja
,
M. L.
Dreher
,
S.
Sadoughi
,
S.
Zhu
, and
T. M.
Keaveny
, “
Relationships among ultrasonic and mechanical properties of cancellous bone in human calcaneus in vitro
,”
Bone
103
,
93
101
(
2017
).
18.
K. A.
Wear
, “
Mechanisms of interaction of ultrasound with cancellous bone: A review
,”
IEEE Trans. Ultrason. Ferroelectr. Freq. Control
67
(
3
),
454
482
(
2020
).
19.
C. F.
Njeh
,
C. M.
Boivin
, and
C. M.
Langton
, “
The role of ultrasound in the assessment of osteoporosis: A review
,”
Osteoporos. Int.
7
(
1
),
7
22
(
1997
).
20.
E. V.
McCloskey
,
J. A.
Kanis
,
A.
Odén
,
N. C.
Harvey
,
D.
Bauer
,
J.
González-Macias
, and
H.
Johansson
, “
Predictive ability of heel quantitative ultrasound for incident fractures: An individual-level meta-analysis
,”
Osteoporos. Int.
26
,
1979
1987
(
2015
).
21.
C. M.
Langton
,
S. B.
Palmer
, and
R. W.
Porter
, “
The measurement of broadband ultrasonic attenuation in cancellous bone
,”
Eng. Med.
13
(
2
),
89
91
(
1984
).
22.
G. W.
Petley
,
P. A.
Robins
, and
J. D.
Aindow
, “
Broadband ultrasonic attenuation: Are current measurement techniques inherently inaccurate?
,”
Br. J. Radiol.
68
(
815
),
1212
1214
(
1995
).
23.
K. A.
Wear
, “
The effect of phase cancellation on estimates of broadband ultrasound attenuation and backscatter coefficient in human calcaneus in vitro
,”
IEEE Trans. Ultrason, Ferroelectr. Freq. Control
55
(
2
),
384
390
(
2008
).
24.
K. A.
Wear
, “
The effect of phase cancellation on estimates of calcaneal broadband ultrasound attenuation in vivo
,”
IEEE Trans. Ultrason, Ferroelectr. Freq. Control
54
(
7
),
1352
1359
(
2007
).
25.
A. Q.
Bauer
,
C. C.
Anderson
,
M. R.
Holland
, and
J. G.
Miller
, “
Measurement artifacts in sonometry of cancellous bone: The relative impact of phase cancellation and interference on measurements of phase-distorting phantoms
,” in
2008 IEEE Ultrasonics Symposium
, Beijing, China (
IEEE
, Piscataway, NJ,
2008
), pp.
137
141
.
26.
J.
Cheng
,
F.
Serra-Hsu
,
Y.
Tian
,
W.
Lin
, and
Y.-X.
Qin
, “
Effects of phase cancellation and receiver aperture size on broadband ultrasonic attenuation for trabecular bone in vitro
,”
Ultrasound Med. Biol.
37
(
12
),
2116
2125
(
2011
).
27.
C. M.
Langton
, “
The 25th anniversary of BUA for the assessment of osteoporosis: Time for a new paradigm
,”
Proc. Inst. Mech. Eng., Part H
225
(
2
),
113
125
(
2011
).
28.
C. M.
Langton
,
M.-L.
Wille
, and
M. B.
Flegg
, “
A deconvolution method for deriving the transit time spectrum for ultrasound propagation through cancellous bone replica models
,”
Proc. Inst. Mech. Eng., Part H
228
(
4
),
321
329
(
2014
).
29.
C. M.
Langton
and
M.-L.
Wille
, “
Experimental and computer simulation validation of ultrasound phase interference created by lateral inhomogeneity of transit time in replica bone: Marrow composite models
,”
Proc. Inst. Mech. Eng., Part H
227
(
8
),
890
895
(
2013
).
30.
C. M.
Langton
and
M.-L.
Wille
, “
Application of ultrasound transit time spectroscopy to human cancellous bone for derivation of bone volume fraction in-vitro
,”
J. Acoust. Soc. Am.
137
(
4
),
2285
2285
(
2015
).
31.
M.-L.
Wille
and
C. M.
Langton
, “
Solid volume fraction estimation of bone: Marrow replica models using ultrasound transit time spectroscopy
,”
Ultrasonics
65
,
329
337
(
2016
).
32.
S. M.
Al-Qahtani
and
C. M.
Langton
, “
Estimation of liquid volume fraction using ultrasound transit time spectroscopy
,”
Meas. Sci. Technol.
27
(
12
),
125003
(
2016
).
33.
A. H.
Alomari
,
M.-L.
Wille
, and
C. M.
Langton
, “
Bone volume fraction and structural parameters for estimation of mechanical stiffness and failure load of human cancellous bone samples; in-vitro comparison of ultrasound transit time spectroscopy and X-ray μCT
,”
Bone
107
,
145
153
(
2018
).
34.
B. K.
Hoffmeister
,
A. R.
Wilson
,
M. J.
Gilbert
, and
M. E.
Sellers
, “
A backscatter difference technique for ultrasonic bone assessment
,”
J. Acoust. Soc. Am.
132
(
6
),
4069
4076
(
2012
).
35.
J. P.
Karjalainen
,
J.
Töyräs
,
O.
Riekkinen
,
M.
Hakulinen
, and
J. S.
Jurvelin
, “
Ultrasound backscatter imaging provides frequency-dependent information on structure, composition and mechanical properties of human trabecular bone
,”
Ultrasound Med. Biol.
35
(
8
),
1376
1384
(
2009
).
36.
C.
Liu
,
F.
Xu
,
D.
Ta
,
T.
Tang
,
Y.
Jiang
,
J.
Dong
, and
W. Q.
Wang
, “
Measurement of the human calcaneus in vivo using ultrasonic backscatter spectral centroid shift
,”
J. Ultrasound Med.
35
(
10
),
2197
2208
(
2016
).
37.
D.
Ta
,
W.
Wang
,
K.
Huang
,
Y.
Wang
, and
L. H.
Le
, “
Analysis of frequency dependence of ultrasonic backscatter coefficient in cancellous bone
,”
J. Acoust. Soc. Am.
124
(
6
),
4083
4090
(
2008
).
38.
B. K.
Hoffmeister
,
P. L.
Spinolo
,
M. E.
Sellers
,
P. L.
Marshall
,
A. M.
Viano
, and
S.-R.
Lee
, “
Effect of intervening tissues on ultrasonic backscatter measurements of bone: An in vitro study
,”
J. Acoust. Soc. Am.
138
(
4
),
2449
2457
(
2015
).
39.
K.
Il Lee
and
M.
Joo Choi
, “
Frequency-dependent attenuation and backscatter coefficients in bovine trabecular bone from 0.2 to 1.2 MHz
,”
J. Acoust. Soc. Am.
131
(
1
),
EL67
EL73
(
2012
).
40.
B. K.
Hoffmeister
, “
Frequency dependence of apparent ultrasonic backscatter from human cancellous bone
,”
Phys. Med. Biol.
56
(
3
),
667
683
(
2011
).
41.
C.
Liu
,
B.
Li
,
Q.
Diwu
,
Y.
Li
,
R.
Zhang
,
D.
Ta
, and
W. Q.
Wang
, “
Relationships of ultrasonic backscatter with bone densities and microstructure in bovine cancellous bone
,”
IEEE Trans. Ultrason, Ferroelectr. Freq. Control
65
(
12
),
2311
2321
(
2018
).
42.
G.
Landi
and
F.
Zama
, “
The active-set method for nonnegative regularization of linear ill-posed problems
,”
Appl. Math. Comput.
175
(
1
),
715
729
(
2006
).
43.
C.
Simon
,
J.
Shen
,
R.
Seip
, and
E. S.
Ebbini
, “
A robust and computationally efficient algorithm for mean scatterer spacing estimation
,”
IEEE Trans. Ultrason, Ferroelectr. Freq. Control
44
(
4
),
882
894
(
1997
).
44.
C.
Liu
,
R.
Dong
,
B.
Li
,
Y.
Li
,
F.
Xu
,
D.
Ta
, and
W.
Wang
, “
Ultrasonic backscatter characterization of cancellous bone using a general Nakagami statistical model
,”
Chin. Phys. B
28
(
2
),
024302
(
2019
).
45.
K.
Huang
,
D.
Ta
,
W.
Wang
, and
L. H.
Le
, “
Simplified inverse filter tracking algorithm for estimating the mean trabecular bone spacing
,”
IEEE Trans. Ultrason. Ferroelectr. Freq. Control
55
(
7
),
1453
1464
(
2008
).
46.
L. L.
Fellingham
and
F. G.
Sommer
, “
Ultrasonic characterization of tissue structure in the in vivo human liver and spleen
,”
IEEE Trans. Sonics Ultrason.
31
(
4
),
418
428
(
1984
).
47.
J. A.
Evans
and
M. B.
Tavakoli
, “
Ultrasonic attenuation and velocity in bone
,”
Phys. Med. Biol.
35
(
10
),
1387
1396
(
1990
).
48.
K. A.
Wear
, “
Ultrasonic scattering from cancellous bone: A review
,”
IEEE Trans. Ultrason. Ferroelectr. Freq. Control
55
(
7
),
1432
1441
(
2008
).
49.
B. K.
Hoffmeister
,
M. R.
Smathers
,
C. J.
Miller
,
J. A.
McPherson
,
C. R.
Thurston
,
P. L.
Spinolo
, and
S. R.
Lee
, “
Backscatter difference measurements of cancellous bone using an ultrasonic imaging system
,”
Ultrason. Imaging
38
(
4
),
285
297
(
2016
).
50.
G.
Iori
,
J.
Du
,
J.
Hackenbeck
,
V.
Kilappa
, and
K.
Raum
, “
Estimation of cortical bone microstructure from ultrasound backscatter
,”
IEEE Trans. Ultrason. Ferroelectr. Freq. Control
68
(
4
),
1081
1095
(
2021
).
51.
B. K.
Hoffmeister
,
S. I.
Delahunt
,
K. L.
Downey
,
A. M.
Viano
,
D. M.
Thomas
,
L. A.
Georgiou
, and
G.
Pirro
, “
In vivo comparison of backscatter techniques for ultrasonic bone assessment at the femoral neck
,”
Ultrasound Med. Biol.
48
(
6
),
997
1009
(
2022
).
52.
W.
Lin
,
Y.-X.
Qin
, and
C.
Rubin
, “
Ultrasonic wave propagation in trabecular bone predicted by the stratified model
,”
Ann. Biomed. Eng.
29
(
9
),
781
790
(
2001
).
53.
R.
Hodgskinson
,
C.
Njeh
,
M.
Whitehead
, and
C.
Langton
, “
The non-linear relationship between BUA and porosity in cancellous bone
,”
Phys. Med. Biol.
41
(
11
),
2411
2420
(
1996
).
54.
B. K.
Hoffmeister
,
A. J.
Gray
,
P. C.
Sharp
,
L. C.
Fairbanks
, and
J.
Huang
, “
Ultrasonic bone assessment using the backscatter amplitude decay constant
,”
Ultrasound Med.
46
(
9
),
2412
2423
(
2020
).
55.
B.
Diedenhofen
and
J.
Musch
, “
cocor: A comprehensive solution for the statistical comparison of correlations
,”
PLoS One
10
(
6
),
e013499
(
2015
).
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