UTE for Fracture Detection & Age Evaluation
Jiang Du1
1University of California, San Diego, United States

Synopsis

Keywords: Musculoskeletal: Skeletal, Image acquisition: Quantification, Image acquisition: Sequences

This lecture talks about recent technical developments in ultrashort echo time (UTE) magnetic resonance imaging and applications in fracture detection and age evaluation. A series of techniques have been developed for high contrast imaging of cortical and trabecular bone. Quantitative UTE techniques have also been developed for mapping of T1, T2*, magnetization transfer ratio (MTR), MT modeling of macromolecular fraction (MMF), quantitative susceptibility mapping (QSM) of bone susceptibility, as well as total, bound, and free water in bone. Applications in fraction detection and age evaluation are also discussed.

1. Introduction

Osteoporosis (OP) is a metabolic bone disease that affects more than 10 million people in the USA and leads to over two million fractures every year – more than heart attacks, strokes, and breast cancer combined (1). The disease results in serious long-term disability and death in a large number of patients. About 80% of the skeleton is cortical bone, and about 80% of all fractures in old age arise at sites that are mainly cortical (2). As a result, it is important to ‘understand’ cortical bone structure and to develop techniques to evaluate it. It is also important to develop techniques to image and assess trabecular bone structure and mechanical properties for improved fracture detection and age evaluation.
Magnetic resonance imaging (MRI) allows non-invasive assessment of protons in soft tissues, but cortical bone has a short T2* and is typically regarded as ‘invisible’ when it is studied with conventional clinical pulse sequences with echo times (TEs) of a few milliseconds or longer (3). Current research often focuses on trabecular bone with indirect imaging of either the yellow or red bone marrow and not direct imaging of bone itself (4). The lack of direct signal from bone makes it impossible to quantify the MR relaxation times (e.g., T1, T2*), magnetization transfer ratio (MTR), and volume concentration of the different water compartments in cortical and trabecular bone (5). Ultrashort echo time (UTE) sequences with TEs of 0.1 ms or shorter allow direct imaging of cortical and trabecular bone (3). In this lecture, we will introduce a series of techniques for morphological and quantitative imaging of bone and applications in fraction detection and age evaluation.

2. Technical Development in Morphological UTE Imaging

Different contrast mechanisms have been developed for bone imaging.
2.1. Dual echo UTE imaging with echo subtraction: Bone contrast is acquired by subtracting a second echo from a first one (3). Rescaled subtraction (6), where the first UTE FID image is scaled down to lower signal from long-T2 tissues in the first compared to the second echo, works more efficiently in creating high positive contrast for cortical bone.
2.2. UTE imaging with long T2 saturation: Saturation pulses have been employed to suppress long T2 tissue signals (6-9). A long 90° pulse can be used with a large spoiling gradient to suppress long T2 tissues, leaving bone to be subsequently detected by UTE data acquisition.
2.3. UTE imaging with off-resonance saturation: UTE imaging with off-resonance saturation contrast (UTE-OSC) employs a high-power saturation pulse placed a few kHz off the water peak to preferentially saturate signals from bone, leaving long T2 muscle and fat signals largely unaffected (10). Subtraction of UTE images with off-resonance saturation from basic UTE images can effectively suppress signals from muscle and fat, creating high bone contrast.
2.4. UTE imaging with adiabatic inversion recovery: The adiabatic inversion recovery UTE (IR-UTE) contrast mechanism employs a long adiabatic inversion pulse to invert the longitudinal magnetizations of long-T2 water (e.g., muscle) and fat (3). The duration of the adiabatic inversion pulse is much longer than bone T2*. As a result, the longitudinal magnetizations of muscle and marrow fat are fully inverted, while the bone magnetization is not inverted but largely saturated. The UTE data acquisition starts at an inversion time (TI) adjusted so that the inverted long T2 magnetizations approach the null points, leaving the bone magnetization being selectively detected by UTE data acquisition. The adiabatic inversion pulse has a relatively broad spectral bandwidth, thereby insensitive to B1 and B0 inhomogeneities, providing robust high contrast imaging of bone (11-14).
2.5. UTE imaging with double adiabatic inversion recovery: The double adiabatic inversion recovery UTE sequence (double-IR-UTE) employs two identical adiabatic inversion pulses (duration of ~6 ms) to sequentially invert the longitudinal magnetizations of long T2 tissues (15). The two adiabatic inversion pulses are applied with pre-defined inversion times TI1, which is the time between the centers of the two inversion pulses, and TI2, which is the time from the center of the second inversion pulse to the center spoke of the multispoke acquisition. Robust long T2 suppression can be achieved by timing the center spoke at the null point. Bone magnetization is not inverted but saturated by the two long adiabatic inversion pulses, recovers after the second TI2, and is subsequently detected by UTE data acquisition.
2.6. UTE with relaxation parameter contrast and subtraction: UTE data acquisition can be combined with relaxation-parameter contrast (16), which exploits the sensitivity of bone proton magnetization to both T2 and RF pulse duration. The RF pulse duration and amplitude can be changed to adjust the relaxation dependence of bone contrast. Two UTE datasets with similar imaging parameters but different RF excitation pulses are acquired. Bone contrast is created by subtraction of the two UTE images.
2.7. Dual-RF and dual-echo (DURANDE) UTE with subtraction: the 3D dual-RF and dual-echo (DURANDE) UTE sequence together with bone-selective image reconstruction has been proposed for rapid bone imaging (17). This technique acquires two dual-echo UTE datasets following short and long RF pulses, with encoding gradients varying continuously along the entire pulse train to halve the total imaging time. The DURANDE UTE sequence employs two rectangular RF pulses (RF1 and RF2), differing in duration and amplitude but having the same pulse area applied alternately in successive TR periods along the entire pulse train. Two echoes at a short TE (TE1) and a long TE (TE2) are collected from the beginning of the gradient ramp-up within each TR. As a result, four echoes are produced and combined via a view-sharing (VS) approach to generate two independent k-space datasets during image reconstruction. Accelerated UTE bone imaging can be achieved by using the sparsity of bone voxels in the corresponding subtraction images.
2.8. Zero echo time (ZTE) imaging of cortical bone: ZTE employs a short rectangular pulse excitation followed by readout gradient flat-top sampling to minimize the effective TE. The repetition time (TR) is minimized to speed up data acquisition. Small flip angle (1-2°) is used to minimize T1 contrast. Higher receiver bandwidths (62.5-83.3 kHz) are recommended to mitigate chemical shift artifacts. Bias field correction, contrast inversion, and background segmentation are employed for CT-like bone contrast (18).
2.9. Short TR adiabatic inversion recovery UTE (STAIR-UTE): In this contrast mechanism, 3D IR-UTE data are acquired with a short TR and a high flip angle within specific absorption rate (SAR) limits for clinical imaging (19). The short TR and TI combination is selected to achieve robust suppression of long-T2 muscle and marrow fat regardless of their different T1 values. Multiple spokes are acquired for efficient volumetric imaging of cortical and trabecular bone. The STAIR-UTE sequence is more efficient than other UTE or ZTE techniques in selective imaging of trabecular bone.

3. Technical Development in Quantitative UTE Imaging

A series of quantitative UTE imaging techniques have been developed to measure T1, T2*, MTR, MMF, QSM, as well as total, bound, and free water in bone.
3.1. Bone T1 mapping: a series of actual flip angle imaging (AFI) based techniques, including variable TR (AFI-VTR) and variable flip angle (AFI-VFA), are developed for accurate bone T1 mapping (20-24).
3.2. Bone T2* mapping: UTE acquisitions at different TEs have been proposed for mono-component, bi-component, and tri-component analysis of cortical bone (25-27). Long T2 suppressed UTE sequences (e.g., IR-UTE or STAIR-UTE) have also been developed to map bone T2*.
3.3. Bone MTR mapping: UTE combined with MT preparation pulse can be used to map MTR of cortical bone. MTR has been shown to be highly correlated with micro-CT porosity and bone biomechanics (28).
3.4. Bone MMF mapping: UTE-MT data together with signal allows simultaneous mapping of MMF and exchange rates. MMF has been shown to be highly correlated with the collagen matrix and mechanical properties of cortical bone (29-32).
3.5. Bone QSM mapping: UTE quantitative susceptibility mapping (UTE-QSM) has been developed to map bone susceptibility. Bone QSM has been shown to be highly correlated with bone mineral density (BMD) (33-35).
3.6. Bone perfusion: Dynamic UTE imaging has been developed to evaluate perfusion in cortical bone (36,37).
3.7. Bone water quantification: UTE, IR-UTE, and UTE-MT techniques have been developed to map total water, bound water, pore water, and collagen backbone protons in cortical bone (38-45).

4. Applications in fraction detection and age evaluation

4.1. UTE measured pore water is highly correlated with cortical porosity and bone mechanical properties: A series of studies have demonstrated significant correlations between UTE measured pore water content with micro-CT porosity and mechanical properties from 4-point bending test (40, 42, 46). These results suggest that UTE can evaluate cortical porosity and bone biomechanics.
4.2. UTE measured bound water is highly correlated with bone organic matrix density and mechanical properties: A series of studies have demonstrated significant correlations between UTE measured bound water content with organic matrix density and bone mechanical properties (40, 46). These results suggest that UTE can evaluate the organic matrix density in bone and its biomechanics.
4.3. UTE-MT measured MTR is highly correlated with bone porosity and mechanical properties: UTE MTR can indirectly assess collagen backbone protons, providing information about cortical porosity and mechanical properties. MTR determined with the UTE-MT sequence provides quantitative information on cortical bone and is sensitive to μCT porosity and biomechanical function (28).
4.4. UTE-MT measured MMF is highly correlated with bone mechanical properties: UTE-MT measured MMF can assess mechanical failures post bone stress injury, which is difficult to evaluate using other techniques (44,45).
4.5. UTE measured T1 is highly correlated with age: A series of studies have demonstrated a significant linear correlation between UTE measured bone T1 relaxation time with age, which leads to increased porosity and more pore water and, therefore, longer T1 values in older subjects (42,47,48).
4.6. UTE perfusion is associated with bone remodeling and fracture repair: Bone is highly vascularized, with a strong association between bone perfusion, bone remodeling, and fracture repair (49). Both increased cortical bone turnover and inflammation are associated with increased blood flow (50). Perfusion plays an important role in the growth and development of bone as well as in disease and healing. UTE can be used to evaluate bone perfusion (36,37). There is an extensive enhancement in blood vessels due to fracture of the tibial plateau two days after injury, with specific enhancement of the periosteum distinguished from that of blood vessels (36).
4.7. ZTE provides “CT-like” contrast for bone fracture detection: ZTE has been used to visualize cortical bone and intraosseous lesions that are occult using CT (18). A recent study demonstrated that cysts seen with ZTE differed from the subchondral ganglion cysts identified during grading, which were confirmed in patients’ standard-of-care MRI examinations (18).

5. Conclusion

A series of UTE techniques have been developed for high contrast morphological imaging of cortical and trabecular bone. Quantitative UTE techniques have also been developed to map T1, T2*, MTR, MMF, susceptibility, and total, bound, and free water in bone. UTE techniques can be used to evaluate bone fracture and aging.

Acknowledgements

Acknowledgements: The author acknowledges grant support from National Institutes of Health (R01AR068987).

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Proc. Intl. Soc. Mag. Reson. Med. 32 (2024)