REVIEW

published: 29 September 2020

doi: 10.3389/fendo.2020.555756

An Update in Qualitative Imaging of

Bone Using Ultrashort Echo Time
Magnetic Resonance
Saeed Jerban 1, Douglas G. Chang 2, Yajun Ma 1, Hyungseok Jang 1, Eric Y. Chang 1,3
and Jiang Du 1*
1 Department of Radiology, University of California, San Diego, San Diego, CA, United States, 2 Departments of Orthopaedic

Surgery, University of California, San Diego, San Diego, CA, United States, 3 Research Service, Veterans Affairs San Diego
Healthcare System, San Diego, CA, United States

Bone is comprised of mineral, collagenous organic matrix, and water. X-ray-based

techniques are the standard approach for bone evaluation in clinics, but they are
unable to detect the organic matrix and water components in bone. Magnetic
resonance imaging (MRI) is being used increasingly for bone evaluation. While MRI can
non-invasively assess the proton pools in soft tissues, cortical bone typically appears as a
Edited by:
Roland Krug, signal void with clinical MR techniques because of its short T2*. New MRI techniques have
University of California, San Francisco, been recently developed to image bone while avoiding the ionizing radiation present in x-
United States
ray-based methods. Qualitative bone imaging can be achieved using ultrashort echo time
Reviewed by:
Sophia Kronthaler,
(UTE), single inversion recovery UTE (IR-UTE), dual-inversion recovery UTE (Dual-IR-UTE),
Technical University of Munich, double-inversion recovery UTE (Double-IR-UTE), and zero echo time (ZTE) sequences.
Germany
The contrast mechanisms as well as the advantages and disadvantages of each
Misung Han,
University of California, San Francisco, technique are discussed.
United States
Keywords: cortical bone, trabecular bone, MRI, UTE–ultra-short TE, single inversion recovery UTE, zero echo
*Correspondence: time MRI
Jiang Du
[email protected]

Specialty section: BACKGROUND

This article was submitted to
Bone Research, Osteoporosis (OP) is a bone disease which affects millions of people around the world (1) and can
a section of the journal lead to serious long-term disability in many patients. OP development always occurs in synchrony
Frontiers in Endocrinology with increases in cortical bone porosity and with trabecular bone deterioration (2). The
Received: 26 April 2020 development of non-invasive imaging techniques to evaluate bone structural properties and
Accepted: 11 September 2020 stability is crucial to improved diagnosis of OP and monitoring of OP patients undergoing
Published: 29 September 2020 medical treatments.
Citation: Bone is a highly complex hierarchical structure (3) of organic matrix combined with
Jerban S, Chang DG, Ma Y, Jang H, hydroxyapatite calcium phosphate (HA) crystals. From the architectural point of view, cortical
Chang EY and Du J (2020)
bone (compact) and trabecular bone (spongy) are two main morphologies of the bone tissue with
An Update in Qualitative Imaging
of Bone Using Ultrashort Echo
approximate porosities under 20% and over 80%, respectively (2, 4). Cortical bone comprises
Time Magnetic Resonance. around 80% of human bone mass (5, 6). Trabecular bone generally exists surrounded by cortical
Front. Endocrinol. 11:555756. bone near joints. Despite large pores in trabecular bone sites, most cortical porosities are limited to
doi: 10.3389/fendo.2020.555756 pores below 100 µm in size (7, 8).

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Jerban et al. Qualitative UTE MRI of Bone

Water in cortical and trabecular bone exist in different states signal when using conventional clinical pulse sequences with
and at various locations (7, 9). In healthy bone, the main portion echo times (TEs) of a several milliseconds or longer (24, 25). The
of water exists in “bound” form to HA crystals and to the lack of direct signal originating from bone impairs the ability of
collagenous matrix (6, 8, 10). The remaining water volume in conventional MRI sequences to provide any qualitative or
bone resides in pores ranging from sub-microns to hundreds of quantitative bone assessments. It should be noted that MRI has
micrometers in size (7, 8). Bound water indicates the bone mineral been used in the past to measure bone microstructure via
and collagenous matrix, while pore water indicates the porosity of indirect visualization of the dark regions (bone) in high-
bone (11, 12). Average bound water T2* is approximately 300 µs resolution conventional acquisitions, however, this approach is
whereas pore water T2* is longer than 1,000 µs and can reach up to limited to distal bone sites and is very motion-sensitive (9, 26).
several milliseconds (10, 13–15). Collagen protons have extremely Recently, new MRI techniques such as ultrashort echo time
short T2*s, on the order of several microseconds (10). (UTE)-MRI have been developed for direct bone imaging and
Bone mineral density (BMD) measurement has been the associated quantitative measurements (5, 6, 16, 22).
standard bone evaluation method in clinics performed using Qualitative bone imaging can be achieved using conventional,
x-ray-based techniques including dual-energy x-ray absorptiometry ultrashort echo time (UTE), adiabatic inversion recovery UTE (IR-
(DEXA) and quantitative computed tomography (QCT) (2, 16, UTE), dual-inversion recovery UTE (Dual-IR-UTE), double-
17). DEXA-based measurement of BMD is non-reliable due to inversion recovery UTE (Double-IR-UTE), UTE with rescaled
very low resolution and its 2D nature. BMD as a predictive echo subtraction (UTE-RS), Fat suppression UTE, Water- and fat-
clinical measurement is quite limited in its representation of suppressed proton projection imaging (WASPI), and zero echo
bone microstructure and, consequently, of bone fragility, time (ZTE) sequences. The contrast mechanisms as well as the
functionality, and fracture risk (18–21). However, these non- advantages and disadvantages of each technique are discussed in
mineral components may describe the bone microstructural and detail. A brief comparison between discussed MRI techniques is
biomechanical properties independently from BMD. Although, presented in Table 1. This review will be an update to our
QCT enables the measurement of bone microstructure in previously published review paper in 2013 (6). As UTE-MRI
addition to BMD however it comes with a high radiation dose. bone imaging field is experiencing fast growth, it is believed that
Employing magnetic resonance imaging (MRI) for bone revisiting this review topic would be benedictional to bone
evaluation has been increasingly reported in the literature. imaging society.
MRI-based techniques for bone evaluation avoid the potential
harm associated with x-ray-based imaging techniques (5, 6, 16,
22). MRI-based bone evaluation can also provide valuable UTE AND IR-UTE PULSE SEQUENCES
evaluation of the surrounding soft tissues including tendons AND THEIR CONTRAST MECHANISM
(23) and muscles, advantages that are not available in x-ray-
based techniques. Bone has a short apparent transverse Both UTE and IR-UTE sequences have been developed for
relaxation time (T2*) and is typically visualized with a void imaging of cortical and trabecular bone as described in the

TABLE 1 | Comparing qualitative MRI techniques for bone imaging.

MRI technique Relative Visualized Contrast Cortical or B0 B1 Scan Appropriate for

bone signal proton pool trabecular sensitivity sensitivity time-efficiency* axial bone sites
bone (e.g., spine, pelvis)

Conventional FSE (27) Very Low Water in large High (reverse Partial cortical Insensitive Insensitive High High
pores contrast) bone
Conventional STE (28) Very Low Water in large High (reverse Partial cortical Sensitive Insensitive High High
pores contrast) bone
Basic UTE (6, 8, 10, 13, 15, 29) High Bound and Low Cortical bone Insensitive Insensitive Relatively high High
pore water
IR-UTE (25, 30–39) High Bound water High Cortical and Insensitive Insensitive Low High
trabecular bone
Dual-IR UTE (33, 40, 41) High Bound water High Cortical and Sensitive Insensitive Low Moderate
trabecular bone
Double-IR UTE (42) High Bound water High Cortical and Insensitive Insensitive Low High
trabecular bone
Fat suppression UTE (43–45) High Bound and Moderate Cortical and Sensitive Insensitive Moderate Moderate
pore water trabecular bone
UTE-RS (46, 47) High Bound and High Cortical bone Sensitive Insensitive Moderate Moderate
pore water
WASPI (48–51) High Bound water High Cortical and Sensitive Sensitive Relatively low Moderate
trabecular bone
ZTE (52–56) Moderate (low Bound and Low Cortical bone Insensitive Insensitive Relatively high High
flip angle) pore water

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Jerban et al. Qualitative UTE MRI of Bone

following sections. Representative 3D UTE and IR-UTE sequences UTE (IR-UTE) sequences have been developed for selective
are shown in Figure 1. The basic 3D UTE sequence (Figure 1A) imaging of collagen-bound water (Figure 1C). With the IR-UTE
employs a short radiofrequency (RF) rectangular pulse (duration = sequence, a Silver-Hoult adiabatic inversion pulse (duration = 8.64
26–52 µs) for signal excitation followed by 3D radial ramp ms) is used to invert the pore water longitudinal magnetization.
sampling with minimal nominal TEs of 8 to 50 µs depending on The longitudinal magnetization of bound water with a very short
the hardware. For 3D UTE Cones sequence, sampling is T2* cannot be inverted, but can be largely saturated, by the
performed over a k-space divided into multiple cone shapes adiabatic IR pulse due to major relaxation of bound water
with twisted radial trajectories along each cone. The Cones magnetization during the adiabatic inversion pulse. The UTE
trajectories are more time-efficient than radial trajectories in acquisition is initiated to selectively detect signal from bound
covering 3D k-space (46), and resolve the limitations associated water only after an inversion time (TI) when the inverted pore
with 2D UTE sequences, namely, sensitivity to eddy currents (57). water magnetization approaches the null point (Figure 1D).
Furthermore, the 3D UTE Cones sequence allows anisotropic
fields of view and spatial resolution, resulting in reduced scan
times (58–60). For 2D UTE imaging the rectangular pulse is CONVENTIONAL MR FOR BONE IMAGING
replaced with a half RF pulse for slice selective excitation. Both
bound water and pore water can be detected using the basic UTE Conventional MRI sequences generally visualize the bone tissue
sequences (Figure 1B) (14). Adiabatic inversion recovery prepared with a signal void surrounded by bright signal from adjacent soft

A
B

C D

E F

FIGURE 1 | (A) The 3D UTE and (C) IR-UTE sequences, as well as the contrast mechanisms for imaging of (B) total water and (D) collagen-bound water. The UTE
sequence employs a short rectangular pulse for signal excitation followed by 3D radial ramp sampling with a minimal nominal TE of 8 µs. The schematic time point
for UTE acquisition at TE of 8 µs is shown in B. The IR-UTE sequence employs an adiabatic inversion pulse to invert and null the pore water magnetization. The
collagen-bound water magnetization is not inverted and is detected by the subsequent UTE data acquisition. For 2D UTE and IR-UTE imaging the rectangular pulse
is replaced with a half RF pulse for slice selective excitation. (E) Dual-IR and (F) Double-IR UTE sequences combined with the contrast mechanism for bone imaging
(bound water). The Dual-IR UTE sequence utilizes two adiabatic IR pulses with center frequencies of 0 and −440 Hz with narrow bandwidth of around 500 Hz (fat
frequency offset at 3T) to invert long T2 water and fat, respectively. The Double-IR UTE sequence utilizes two identical adiabatic IR pulses with a center frequency of
−220 Hz with broad bandwidth of no less than 1000 Hz (half of the fat frequency offset at 3T) to invert both long T2 water and fat. Bone signal is largely saturated by
each adiabatic IR pulse due to its fast T2* relaxation during the inversion period. At the optimized TI1 and TI2 in both Dual- and Double-IR UTE sequences, both long
T2 water and fat can be suppressed simultaneously, and the bone signals can be acquired with multiple UTE spokes This figure was partially presented before by
Ma et al. (42). Reprinting permission is granted through Rightslink system. The figure is modified for presentation purposes. Minor modifications were performed for
presentation purposes. RF, radio frequency pulse; TE, echo time; Gx,y,z, gradient magnetic field in X, Y, Z directions; DAW, data acquisition window; Mz, longitudinal
magnetization; Mxy, transverse magnetization; CW, collagen-bound water; PW, pore water; IR, inversion recovery; TI, inversion time.

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Jerban et al. Qualitative UTE MRI of Bone

tissues. Pore water may compose up to a quarter of the bone volume Collagen protons have extremely short T2*s (T2* on the order of
and possesses a short T2* and relatively long T2 (up to 100 ms) (10, several microseconds) and are not detectable, even when using
13–15). Therefore, some conventional fast spin echo (FSE) (27) and UTE MRI sequences. The effective TEs in UTE are significantly
short echo time (STE) c sequences have the potential to image pore longer than the T2*s of collagen backbone protons (≈ 10 µs)
water in cortical bone, even though clinical gradient recalled echo because of the use of a relatively long RF excitation pulse as well as
(GRE) sequences are not capable of pore water imaging, as shown time-consuming ramp sampling (8, 10, 15, 29). UTE MRI imaging
in Figure 2 (Figures 2A, B) and Figure 3A. Consequently, FSE and results in high in vivo signal of bone, but it is still lower than the
STE techniques might be useful in qualitative imaging of highly signal from surrounding soft tissues, which in turn leads to
porous cortical bone sites, which can be found more in elderly relatively low contrast as demonstrated in Figure 3B. Improving
cohorts. Nevertheless, qualitative imaging of cortical bone with low the UTE contrast in bone imaging requires fat suppression in
porosity requires more advanced MR imaging techniques. trabecular bone sites while fat and soft tissue suppression in cortical
bone sites. Moreover, pore water suppression can improve the
cortical bone UTE contrast by imaging only the bound water.
UTE MR BONE IMAGING
UTE MRI sequences with nominal TEs around tens of IR-UTE MR IMAGING OF CORTICAL BONE
microseconds or less can detect signals from both bound water
(T2* ≈ 300 µs) and pore water (T2* > 1,000 µs) pools in cortical Adiabatic inversion recovery (IR) preparation pulses have been
bone, as demonstrated in Figure 2 (Figures 2C, D) (6, 13). suggested in different studies to suppress long T2 tissue components

FIGURE 2 | (A) Conventional fast spin echo (FSE), (B) gradient echo (GRE), (C) 3D ultrashort echo time (3D UTE), (D) 3D adiabatic inversion recovery UTE (3D IR-
UTE) MRI images in axial plane of a piece of human cortical bone harvested from the anterior tibial midshaft. FSE and GRE only detect signal from pore water, likely
in Haversian canals (indicated with yellow arrow). UTE MRI results in high signal from all sites of the bone specimen. IR-UTE detects signal from bone with much
higher contrast than UTE MRI can. his figure was previously presented by Du et al. (13). Reprinting permission is granted through Rightslink system. The figure is
modified for presentation purposes. Minor modifications were performed for presentation purposes.

FIGURE 3 | (A) Conventional gradient echo (GRE), (B) ultrashort echo time (UTE), and (C) adiabatic inversion recovery UTE (IR-UTE) image in axial plane of the
lower leg. GRE results in void signal in bone. UTE MRI results in high signal for bone, but low contrast. IR-UTE results in higher contrast between cortical bone and
surrounding soft tissue, similar to that can be seen in CT. This figure was previously presented by Jerban et al. (61). Reprinting permission is granted through
Rightslink system. The figure is modified for presentation purposes. Minor modifications were performed for presentation purposes. 3D UTE sequence parameters:
FOV = 14×14×14 cm3; voxel size = 0.7×0.7×5 mm3, scan time » 3.2 mins. 3D IR-UTE sequence parameters: FOV = 14×14×14 cm3; voxel size = 0.7×0.7×5 mm3,
TR/TI = 300/110 ms, scan time » 3.5 mins.

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Jerban et al. Qualitative UTE MRI of Bone

and increase the contrast in UTE MR imaging of cortical bone The IR-UTE-based qualitative bone imaging sequence has
(Figure 1). The bound water component in cortical bone can be been applied to different bone sites in vivo such as tibia and fibula
selectively imaged with both 2D and 3D IR-UTE sequences. In both (36–38), radius (36), hip (34), and shoulder (39); however, the
cases, a relatively long adiabatic IR pulse (e.g., Silver-Hoult pulse, contrast and image quality depend on the anatomical location,
8.64 ms in duration) is employed to invert the longitudinal coil quality and size, B0 and B1 homogeneity, bone thickness,
magnetizations of first, long T2 water (e.g., free water image resolution, and slice thickness. These factors affect the
components of cortical bone, and water in muscle) and second, proper visualization of the bone structure, signal to noise ratio
fat in cortical bone and bone marrow (25, 30, 32–34). However, the (SNR), suppression uniformity, and image artifacts. Bone sites in
simultaneous suppression of pore water, fat, and muscle is highly axial skeleton or deeply located in the body such as spine and hip
challenging due to the significant differences between MR are more difficult to be scanned compared with tibia and radius
properties of these three proton pools. Thus, IR-UTE based in peripheral bone sites. Specifically, sophisticated thin bone
imaging of bound water may coexist with some level of pore structure requires high resolution imaging which is highly
water, fat, and muscle contamination. The 2D or 3D UTE data sensitive to motion. Larger required coils result in greater B1
acquisition starts at an inversion time (TI) designed to allow the inhomogeneity and non-uniform suppression. Figure 4
inverted free water and fat longitudinal magnetizations to be at or illustrates coronal images of the hip and femoral head of a
close to the null point (Figure 1) (30). Figure 2 shows a comparison healthy young volunteer using 2D FSE and 3D IR-UTE Cones
between conventional MRI (FSE and GRE), UTE, and IR-UTE sequences (31).
sequences performed on a piece of anterior tibial cortex imaged in
axial plane. The conventional FSE sequence produces higher signal
in cortical bone compared with the GRE sequence, though both
techniques only detect signal from pore water residing in Haversian DUAL-IR-UTE IMAGING OF CORTICAL
canals. The UTE sequence can detect free water in the pores (high BONE
signal with fine structure) and bound water (uniform background
signal). The signal of the fine structure will disappear using the IR- Dual-adiabatic inversion recovery (Dual-IR) pulses can also be
UTE sequence which suppresses the free water signal while the employed to invert and null signals from long T2 water and fat,
uniform background signal from bound water remains. respectively (33). Dual-IR followed by selective UTE imaging can
Figure 3 shows tibial and fibular midshaft bone in a healthy detect bound water in cortical bone and provide qualitative bone
young volunteer imaged with GRE, UTE and IR-UTE sequences. evaluations. In this approach, two successive long adiabatic
In UTE MRI, bone shows as high signal compared with inversion pulses are employed to invert the longitudinal
conventional MRI technique, but as low signal compared with magnetization of long T2 water and long T2 fat, respectively (33,
surrounding tissues such as marrow fat and muscle. The IR-UTE 40, 41). The pulse sequence diagram for Dual-IR-UTE is similar to
technique greatly suppresses signals from both the marrow fat IR-UTE sequence hovers with an additional inversion recovery
and muscle, resulting in visualization of cortical bone with a CT- pulse (Figure 1). As a result of a significant transverse relaxation of
like contrast that can be used for qualitative bone evaluation. cortical bone magnetization with short T2 during the long adiabatic
Adiabatic inversion recovery (AIR) UTE (AIR-UTE) (35, 36) inversion process, its longitudinal magnetization cannot be inverted
is an alternative abbreviation used for abovementioned IR-UTE (62). The UTE MRI data acquisition begins after the first delay time
technique by other groups. AIR-UTE is used to visualize bound (TI1), which is required for the nulling of the inverted long T2 water
water in cortical bone and provide a qualitative image of cortical magnetization, and the second delay time (TI2), which is required
bone structure. for the nulling of the inverted fat magnetization. Figure 5 shows

FIGURE 4 | In vivo imaging of the hip of a 24‐year‐old female volunteer with a (A) clinical 2D T2‐weighted FSE and (B) 3D IR‐UTE Cones sequences. Soft tissues
are well‐suppressed in the 3D IR‐UTE Cones image, while they are bright in the clinical T2‐FSE images. This figure was previously presented by Ma et al. (31).
Reprinting permission is granted through Rightslink system. The figure is modified for presentation purposes. Minor modifications were performed for presentation
purposes. 3D IR-UTE sequence parameters: FOV = 38 cm3 × 38 cm3 × 20 cm3; voxel size = 2.4 mm3 × 2.4 mm3 × 5 mm3, TR/TI = 150/64 ms, and scan time ≈
9.5 min.

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Jerban et al. Qualitative UTE MRI of Bone

representative images of the left distal tibia of a volunteer using IR-UTE utilizes two identical adiabatic inversion pulses. The center
clinical 2D GRE, UTE and Dual-IR-UTE techniques. Cortical bone frequency of these identical pulses are located at the water peak
is visualized with a void signal using the 2D GRE pulse sequence, while their spectral widths are broad enough to cover both water
however with a poor contrast using the basic UTE pulse sequence and fat frequencies (42). These two adiabatic inversion pulses are
because of the significant signals acquired from surrounding muscle applied in sequence with two different inversion times (TI1 and
and fat. The Dual-IR-UTE sequence suppresses long T2 water TI2) in order to invert and null the longitudinal magnetizations of
signals, including those from muscle and free water in bone, as long T2 muscle and fat. Similar to Dual-IR-UTE technique, due to
well as from marrow fat, and displays bound water in cortical bone the significant transverse relaxation of the cortical bone
with high signal and contrast. Dual-IR UTE can be applied to magnetization during the long adiabatic inversion pluses, its
different body regions. However, this technique only works well for longitudinal magnetization cannot be inverted. The pulse
simultaneous water and fat suppression when the frequency offset sequence diagram for Double-IR-UTE is similar to IR-UTE
due to the B0 inhomogeneity is less than half of the bandwidth of sequence hovers with an additional inversion recovery pulse
the used adiabatic IR pulse. (Figure 1). Figure 6 shows representative images of the left distal
tibia of a volunteer using clinical 3D GRE, UTE and Double-IR-
UTE techniques (42). The Double-IR-UTE demonstrated cortical
bone with high signal and contrast as the signal from long T2 water
DOUBLE-INVERSION RECOVERY UTE and fat were suppressed robustly. Notably, bone was visualized with
(DOUBLE-IR-UTE) a signal void using the 3D GRE sequence, and with a poor contrast
using the conventional UTE sequence.
Double inversion recovery (Double-IR) UTE sequence also All the IR-UTE-based techniques (IR-UTE, Dual-IR-UTE,
employs two adiabatic inversion pulses to invert and null signals Double-IR-UTE, and AIR-UTE) appear to provide a uniform
from long T2 tissues (42). Despite Dual-IR-UTE sequence, Double- suppression of long T2 water and fat signals, which in turn

FIGURE 5 | The tibial midshaft of a healthy young volunteer imaged with (A) GRE, (B) UTE and dual adiabatic inversion recovery UTE (Dual-IR-UTE) sequences. The
Dual-IR-UTE image (C) selectively suppresses signal from fat and muscle, and which creates high contrast for cortical bone. This figure was previously presented by
Du et al. (33). Reprinting permission is granted through Rightslink system. The figure is modified for presentation purposes. Minor modifications were performed for
presentation purposes. 2D UTE sequence parameters: FOV = 10 cm2 × 10 cm2; voxel size = 0.2 cm2 × 0.2 cm2 and scan time ≈ 3 min. 3D Dual-IR-UTE sequence
parameters: FOV = 10 cm2 × 10 cm2; voxel size = 0.2×0.2, TR/TI1/TI2 = 300/140/110 ms, and scan time ≈ 3 min.

FIGURE 6 | In vivo imaging of the lower leg of young healthy volunteer using (A) clinical 3D GRE sequence (no signal in cortical bone), (B) the conventional 3D UTE
sequence (detects signal in cortical bone signal but with low contrast), and (C) the 3D Double-IR-UTE sequence which shows simultaneous suppression of muscle
and marrow fat, providing higher contrast between cortical bone and surrounding soft tissue. This figure was previously presented by Ma et al. (42). Reprinting
permission is granted through Rightslink system. The figure is modified for presentation purposes. Minor modifications were performed for presentation purposes. 3D
UTE sequence parameters: FOV = 14 cm3 × 14 cm3 × 12 cm3; voxel size = 0.55 mm3 × 0.55 mm3 × 6 mm3, and scan time ≈ 1.3 min. 3D Double-IR-UTE
sequence parameters: FOV = 14×14×12 cm3; voxel size = 1.1 mm3 × 1.1 mm3 × 6 mm3, TR/TI1/TI2 = 200/100/45 ms, and scan time ≈ 2.9 min.

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Jerban et al. Qualitative UTE MRI of Bone

provides a good qualitative image of the targeted bone. This is chemical shifts and average signal oscillation observed in the
because adiabatic IR pulses are relatively insensitive to B1 and B0 multi-echo MRI in T2 fitting analyses (63). Fat suppression
inhomogeneities (41, 62). techniques can be used to remove fat signal contamination in
To the best of our knowledge, there is no detailed comparison bone assessment and to improve the bone contrast in UTE-MRI.
study for these techniques. Based on our experience, IR-UTE Chemical shift fat saturation (FatSat), soft-hard water excitation,
sequence is more time-efficient than both Dual- and Double-IR and single point Dixon methods have been employed to suppress
UTE sequences. IR- and Double-IR UTE sequences are much less fat in UTE bone imaging (43, 44). FatSat is widely used in clinical
sensitive to the B0 inhomogeneity than Dual-IR UTE sequence. MR sequences, however, it is not suitable for bone imaging due to
Dual-IR sequence provides a better SNR compared with Double- the strong signal saturation of the wide spectrum band of bone. The
IR UTE sequence. It would be interesting to perform a future study soft-hard pulse has been proposed to overcome the signal
to compare all these techniques regarding the performance of attenuation effect via utilizing a low power soft-pulse for fat
SNR, CNR, and the corresponding scan efficiency. The excitation in the opposite direction of the following hard pulse
comparisons presented in Table 1 have been prepared based on (43). Figure 7 shows a comparison between tibial and fibular bone
the practical experience of the authors. image contrast in vivo obtained using basic UTE, FatSat, and the
soft-hard water excitation techniques (43). The fat signal could be
suppressed well using both the soft-hard pulse and the FatSat
FAT SUPPRESSION UTE module in the three illustrated slices. However, the cortical bone
signal (indicated by yellow arrow) were much better preserved in
Human bone exists in combination with bone marrow which the soft-hard excitation images (Figures 7D–F) (43). Single-point
possess high percentage of fat. The fat presence results in Dixon method is a postprocessing method to separate water and fat

FIGURE 7 | In vivo UTE Cones imaging of tibial midshaft of young healthy volunteer using (A–C) a single hard pulse excitation (basic UTE), (D–F) the soft-hard water
excitation pulse, and (G-I) the conventional FatSat module. UTE images are presented in three representative slices. Fat was well suppressed by both the soft-hard
pulse and the FatSat module. The cortical bone and coil elements (indicated by yellow arrows in D–F) were much better preserved in the soft-hard excitation images
(D–F) compared with FatSat images (G–I). This figure was previously presented by Ma et al. (43). The reprinting permission is granted through Rightslink system.
The figure is modified for presentation purposes. Minor modifications were performed for presentation purposes. 3D UTE sequence parameters: FOV = 12 cm3 × 12
cm3 × 16 cm3; voxel size = 0.63 mm3 × 0.63 mm3 × 2 mm3, and scan time ≈ 3.4 min.

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Jerban et al. Qualitative UTE MRI of Bone

signals from a dual-echo UTE acquisition (44). The calculated water WATER- AND FAT-SUPPRESSED
and fat maps can then be used to suppress fat in the UTE image. PROTON PROJECTION IMAGING (WASPI)
OF CORTICAL BONE
UTE WITH RESCALED ECHO Water- and fat-suppressed proton projection MRI (WASPI) is
SUBTRACTION (UTE-RS) another MRI sequence developed for selective imaging of bone
water bound to the organic matrix (48–50). In this technique,
UTE with rescaled echo subtraction (UTE-RS) can provide two long-duration, yet low-power, rectangular RF pulses are used
qualitative imaging of the cortical bone (46, 47). In UTE-RS, the to selectively saturate signals from long T2 water and fat. Since
free induction decay (FID) image is scaled down so that signals from bound water has a short T2*, it will remain largely unsaturated
muscle and fat become lower than those from the second echo (46). and provide qualitative imaging of bound water in bone. Figure
In the subtraction image, signals from muscle and fat are negative, 9 shows bone WASPI images in the wrist joint of a healthy
whereas those from short-T2 species are positive, separating them volunteer in transverse, coronal and sagittal planes (51).
from air which has a signal intensity fluctuating around zero (46).
The UTE-RS technique can be efficient in creating high positive
contrast for short T2 species such as cortical bone. Regular unscaled ZTE BONE IMAGING
echo subtraction may reduce bone contrast in this situation.
Performing UTE-RS in trabecular bone sites would be challenging An alternative approach for bone imaging is the zero echo time
due to the fat presence in bone marrow and signal oscillation. (ZTE) sequence, which employs a short rectangular excitation
Rescaled echo subtraction method has been also used with ZTE pulse during the fully ramped up readout gradient, followed by
technique (64). Figure 8 shows the tibial cortex of a healthy young fast radial sampling (52, 53). Alternatively, frequency-modulated
volunteer imaged in the coronal plane using the UTE-RS technique. pulse with interleaved transmit-receive operation, can also be

FIGURE 8 | Dual-echo 3D UTE imaging of the tibial cortex of a healthy young volunteer in coronal plane with (A) TE = 8 ms and (B) TE = 2.2 ms. (C) Subtraction of
the second echo from the first echo image rescaled down by a factor of 0.4. This figure was previously presented by Du et al. (46). The reprinting permission is
granted through Rightslink system. The figure is modified for presentation purposes. Minor modifications were performed for presentation purposes. 3D UTE
sequence parameters: FOV = 24 × 24 cm3 × 24 cm3; voxel size = 0.8 mm3 × 0.8 mm3× 0.8 mm3, TEs = 0.008/2.2 ms, and scan time ≈ 5.5 min.

FIGURE 9 | In vivo water- and fat-suppressed proton projection imaging (WASPI) of the wrist joint of a healthy volunteer in (A) transverse, (B) coronal and (C)
sagittal slices from the 3D WASPI image dataset. This figure was previously presented by Wu et al. (51). Reprinting permission is granted through Rightslink system.
The figure is modified for presentation purposes. Minor modifications were performed for presentation purposes. 3D WASPI sequence parameters: FOV = 12 cm3 ×
12 cm3 × 12 cm3; voxel size = 0.9 mm3 × 0.9 mm3 × 0.9 mm3, and scan time ≈ 18 min.

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Jerban et al. Qualitative UTE MRI of Bone

used for bone imaging which is known as sweep imaging with filled using a Cartesian single-point imaging technique, which is
Fourier transformation (SWIFT) (54). Eliminating the rapid known as pointwise encoding time reduction with radial
gradient switching between TR intervals results in the decreased acquisition (PETRA) (55). Figure 10 shows representative
acoustic noises during scans and in the reduced eddy current postprocessed ZTE and conventional FSE images of the
artifacts (5). These sequences have the potential to image both shoulder of a young symptomatic patient. CT-like ZTE-based
bound water and pore water in bone. These sequences suffer from image (Figure 11A) was obtained after bias-correction and
a gap of data at the center of k-space as a result of a dead time inverse-logarithmic rescaling (52). The qualitative ZTE bone
caused by the finite RF pulse, transmit-receive switching, and image clearly visualizes the bone fragmentation, which is not
digital bandpass filtering (53). The missing data in the ZTE clear in FSE image (52). To improve the image contrast ZTE
technique can be compensated via oversampled acquisition and techniques has been also used with inversion recovery preparation
mathematical reconstruction (53). The ZTE data gap can be also which suppress long-T2 signal (56).

FIGURE 10 | (A) Zero echo time (ZTE)-based and (B) proton-density-weighted FSE MR imaging of the shoulder of a young symptomatic patient. The CT-like ZTE-
based image (A) is obtained after bias-correction and inverse-logarithmic rescaling (52). Qualitative bone imaging by ZTE shows the bone fragment (indicated with
arrow), which is not clear in FSE image. This figure was previously presented by Breighner et al. (52). Reprinting permission is granted from Radiology journal (RSNA).
The figure is modified for presentation purposes. Minor modifications were performed for presentation purposes. 3D ZTE sequence parameters: FOV = 28 cm3 ×
28 cm3 × 28 cm3; voxel size = 0.87 mm3 × 0.87 mm3 × 1.5 mm3, and scan time ≈ 5 min.

FIGURE 11 | 3D IR-UTE-Cones imaging of (A) the femur/spine and (B) the shoulder sample in the coronal plane, demonstrating high contrast imaging of cortical
and trabecular bone at various sites in the body using a clinical whole-body 3T scanner. 3D IR-UTE sequence parameters for femur/spine: FOV = 45×45×20.8 cm3;
voxel size = 2.5×2.5×4 mm3, TR/TI = 183/78 ms, and scan time » 10 mins. 3D IR-UTE sequence parameters for shoulder: FOV = 20× 20 × 10 cm3; voxel size =
0.8×0.8×2 mm3, TR/TI = 140/61 ms, and scan time » 6 mins. This figure is original and based on data from (31). A version of this figure has been presented before
in ISMRM 2019 conference (poster 3754).

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Jerban et al. Qualitative UTE MRI of Bone

IR-UTE IMAGING OF TRABECULAR BONE CONCLUSIONS

Direct MR imaging of trabecular bone is technically challenging MRI-based qualitative imaging of different water compartments
due to its fast signal decay, the fat presence in bone marrow, and in bone has drawn great interest among musculoskeletal
local field inhomogeneities that are caused by the trabecular bone radiologists and orthopedic researchers. These techniques
structure (24, 45, 65). Recently, UTE sequences and their variants provide simultaneous assessment of bone and the surrounding
(e.g., WASPI and ZTE sequences) have been developed to soft tissues, while avoiding patient exposure to ionizing
directly acquire the signals of phosphorus (66–68) or hydrogen radiation. Since conventional clinical MRI techniques fail to
proton (45, 69, 70) in trabecular bone. Such techniques have been detect signal from bone, here are several qualitative MR
used successfully for phosphorus density and its relaxation times techniques currently being developed for assessment of cortical
assessment in vivo for both cortical and trabecular bone (66–68). bone. Such techniques include UTE MRI, which detects signal
However, further optimization of these techniques for from both bound water and pore water in bone, but with low
translation to clinical investigations is limited because the contrast due to much higher signals from the surrounding soft
required hardware for phosphorus imaging is not available in tissues such as muscle and bone marrow fat. IR-UTE-based
most clinical scanners. sequences provide efficient suppression of long T2 tissues,
Direct hydrogen proton imaging of trabecular bone using allowing bound water imaging with CT-like bone contrast.
WASPI and fat-suppressed UTE techniques have also been Other techniques, such as UTE-RS, WASPI, ZTE and SWIFT
investigated recently (45, 69, 70). Suppressing signals from also have potential for qualitative bone imaging. Some of the
long T2 components in bone marrow is crucial in order to described techniques can be used for quantitative bone imaging
create a high contrast for bone in trabecular sites. WASPI and for microstructural evaluations.
technique uses two hard pulses with narrow frequency bands This study would be greatly improved if the presented MRI
in order to selectively excite water and fat signals. Following the images would be acquired from subjects with bone diseases or
two hard pulses, strong gradient crushers are used to saturate injuries resulting in a better comparison between presented
water and fat signals before data acquisition (48). Wurnig et al. techniques. However, most published results in the literature
employed the UTE sequence to measure T2* of trabecular bone only have covered healthy bone images. Comparison between the
samples, with a SPIR (spectral pre-saturation with inversion presented techniques in Table 1 is largely based on practical
recovery) module to suppress marrow fat (45). These two experience of the authors. Particularly, the scan time efficiency
techniques show promising results for trabecular bone, though was ranked semi-qualitatively, and is affected by acquisition
they are both sensitive to B1 and B0 inhomogeneities, posing parameters (e.g., undersampled acquisition, extended sampling,
clinical challenges for in vivo imaging of trabecular bone in the etc.) and reconstruction algorithms.
hip and spine.
To resolve these issues, a broadband adiabatic inversion
recovery prepared 3D UTE Cones (3D IR-UTE-Cones)
sequence has been proposed for direct volumetric imaging of AUTHOR CONTRIBUTIONS
bone by simultaneous water and fat signal suppression (71)
All authors contributed to the article and approved the
which later being used for direct trabecular bone imaging (31).
submitted version.
The combination of a short repetition time (TR) and inversion
time (TI) is used to achieve robust suppression of different long
T2 tissues with a range of T1s. Employing an adiabatic full
passage (AFP) pulse sequence with a relatively wide bandwidth FUNDING
(~1.5 kHz), the proposed IR preparation is approximately
insensitive to the inhomogeneities of B1 and B0 (72). Figure The authors acknowledge grant support from NIH
11 shows high contrast imaging of trabecular bone in the (R01AR068987, R01AR075825, R01AR062581, R21AR075851)
shoulder, femoral head and neck, as well as the spine with the and VA Clinical Science and Rehabilitation R&D Awards
3D IR-UTE-Cones sequence (31). (I01CX001388 and I01RX002604).

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(UTE) and inversion recovery UTE sequences. NMR BioMed (2016) 29:1373– article distributed under the terms of the Creative Commons Attribution License
80. doi: 10.1002/nbm.3579 (CC BY). The use, distribution or reproduction in other forums is permitted, provided
60. Ma Y, Carl M, Shao H, Tadros AS, Chang EY, Du J. Three-dimensional the original author(s) and the copyright owner(s) are credited and that the original
ultrashort echo time cones T 1r (3D UTE-cones-T 1r ) imaging. NMR publication in this journal is cited, in accordance with accepted academic practice. No
BioMed (2017) 30:e3709. doi: 10.1002/nbm.3709 use, distribution or reproduction is permitted which does not comply with these terms.

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