High contrast cartilaginous endplate imaging in spine using three dimensional dual-inversion recovery prepared ultrashort echo time (3D DIR-UTE) sequence

Low back pain (LBP) is one of the major causes of disability, affecting approximately 25% of adults in the United States [1, 2]. The need for accurate diagnoses as well as focused preventive and therapeutic strategies in this condition have become a major public health priority [3]. Intervertebral disc (IVD) degeneration has been recognized as one of the main causes of chronic low back pain [4]. Many of these cases have been associated with abnormality of the cartilaginous endplate (CEP) [5].

Vertebral endplate structure lies at the cranial and caudal interface of the intervertebral disc on one side and vertebral body, which consists of an osseous component and a hyaline cartilage component (known as the CEP), on the other [6]. The CEP comprised of a hydrated proteoglycan matrix, fortified by an interlaced framework of collagen fibrils, which directly attaches to the intervertebral disc via the lamellae within the inner (medial) annulus fibrosus. No direct connection is found between CEP and the osseous structure of the vertebral bodies [7].

The CEP acts as the nutrient transport bridge from blood vessels to the disc cells, which is of critical importance to maintaining disc health [8, 9]. Degeneration, mineralization, and dehydration of the CEP due to age, injury, and degradation reduce the CEP’s permeability, leading to a diminished capacity for nutrient transport. Thus, the health of the CEP could be highly related to early IVD degeneration and associated LBP.. Moreover, the CEP is also subjected to mechanical loads which are distributed onto adjacent vertebrae as a means to prevent the disc nucleus from bulging under pressure [10]. Damage to this region might present as a painful pathology [11]. Thus, evaluation of the CEP region may be critical for the assessment of LBP and diagnosis of early IVD degeneration.

Magnetic resonance imaging (MRI) is a powerful tool for the diagnosis of IVD degeneration. The most commonly used techniques are the T₁- and T₂-weighted sequences [12]. However, because the CEP has a relatively short transverse relaxation time (T₂: ~ 18 ms, T₂*: ~ 15 ms)) [13, 14], these routine clinical sequences cannot detect sufficient CEP signals for direct imaging or quantification, thus limiting the effectiveness of MRI for early evaluation of IVD degeneration.

Ultrashort echo time (UTE) sequences with echo times shorter than 100 µs are able to detect many short T₂ tissues, such as the CEP, tendons, and bone, positioning this type of sequence as a promising approach to image and evaluate those tissues [15, 16]. Recently, several UTE techniques have been developed for long T₂ suppression and selective imaging of short T₂ tissues, such as dual-echo UTE with subtraction [17], T₁-weighted fat-saturated UTE (T_1w-FS-UTE) [18], inversion recovery-prepared and fat-saturated UTE (IR-FS-UTE) [19], and dual inversion recovery-prepared UTE (DIR-UTE) [20] sequences. The dual-echo UTE is a fast technique but suffers from low contrast-to-noise ratio (CNR) between the CEP and bone marrow fat (BMF) due to the relatively fast T₂* decay of BMF [21]. The fast T_1w-FS-UTE sequence has been applied for high-contrast imaging of the osteochondral junction (OCJ) with better contrast between the CEP and BMF than the dual-echo subtraction method [18]. Moreover, the UTE sequences which incorporate adiabatic inversion, such as IR-FS-UTE, are very efficient in generating high contrast between short and long T₂ tissues [19, 20, 22‐24] and have been used for high contrast imaging of the OCJ [25]. Such techniques can aid in imaging the CEP with high resolution [19]. In CEP imaging, the IR-FS-UTE sequence can produce a very high contrast between the CEP and nucleus pulposus (NP), but the contrast between the CEP and BMF is limited because of the chemical fat saturation (FatSat) module that prohibits efficient fat suppression if more acquisition spokes are used in a repetition time (TR). This inefficient fat suppression can be overcome by replacing the FatSat module with another adiabatic inversion pulse that is centered on the fat frequency, i.e., the DIR-UTE technique [20]. The DIR-UTE sequence has been shown to generate a very high image contrast for the OCJ region with efficient suppression of signals from both the long T₂ cartilage and marrow fat [20].

In this study, we aim to image the CEP instead of the bony endplate. Bony endplate and subchondral bone structures are dark in the proposed DIR-UTE images because cortical bone typically has a much lower proton density than cartilage tissues including the CEP [26, 27]. Given the advantages of DIR-UTE sequence in imaging of short T₂ tissues, we proposed to further optimize it for high contrast imaging of CEP in the human lumbar spine, and compare its performance with other established UTE techniques, namely IR-FS-UTE, T_1w-FS-UTE, and FS-UTE.

Supplemental Information Fig. 1 shows the DIR-UTE images acquired from a 32-year-old asymptomatic male volunteer at various TI combinations. To optimize the image contrast between CEP and NP, TI₁ varies from 580 to 640 ms while TI₂ is fixed at 150 ms. Similarly, to optimize the contrast between CEP and BMF, TI₂ varies from 125 to 175 ms while TI₁ is fixed at 610 ms. As can be seen from the figure, the images resulting from these different TI combinations all show good CEP contrast visually, proving that the DIR-UTE technique can effectively highlight the CEP region over a wide range of TI₁s and TI₂s. This demonstrates the robustness of the DIR-UTE technique for high contrast imaging. Supplemental Information Table 1 lists the measured CNR_CEP-NP and CNR_CEP-BMF values for the images shown in Supplemental Information Fig. 1. When TI₂ is fixed at 150 ms, the CNR_CEP-NP values increase from 17.8 to 19.0, then decrease to 17.9 when TI₁ increases from 580 to 640 ms. In addition, when TI₁ is fixed at 610 ms, the CNR_CEP-BMF values increase from 17.0 to 17.6, then decrease to 15.9 when TI₂ increases from 125 to 175 ms. The highest CNR_CEP-NP and CNR_CEP-BMF values are achieved when TI₁ = 610 ms and TI₂ = 150 ms. These optimized TIs were employed for the subsequent DIR-UTE imaging of both asymptomatic volunteers and patients.

Figure 2 shows the representative lumbar spine images from two asymptomatic volunteers. The CEP signal cannot be efficiently captured in the clinical fat suppressed T_2w-FSE sequence owing to its relatively short T₂ relaxation time, whereas it is clearly seen on all UTE images. The DIR-UTE, IR-FS-UTE, and T_1w-FS-UTE sequences all produce higher CEP contrast than the regular FS-UTE sequence because of their higher T₁-weighting property. The DIR-UTE images show the best CEP contrast for visual comparison.

Table 1 summarizes the measured CNR_CEP-NP and CNR_CEP-BMF values of all four UTE sequences for the six asymptomatic volunteers. Of the different sequences used, the DIR-UTE presents the highest CEP contrast for CEP vs. NP (23.1 ± 1.7) and CEP vs. BMF (19.9 ± 3.0), followed by IR-FS-UTE, T_1w-FS-UTE, and FS-UTE. The DIR-UTE showed significantly higher CNRs in both CNR_CEP-NP and CNR_CEP-BMF compared to IR-FS-UTE (p = 0.0005, p = 0.0109), T_1w-FS-UTE (p = 0.0017, p = 0.0003), and FS-UTE (p = 0.0010, p = 0.0008) respectively.

Results from the ex vivo sample study are presented in Fig. 3. As seen from Fig. 3C, signals from long T₂ water and fat are well suppressed by the DIR technique. The high-intensity band of CEP demonstrates a thickness from 0.6 mm to 1.2 mm. In comparison, the CEP is dark in both clinical T_2w- and T_1w-FSE images due to its short T₂. The lower level of this disc is particularly interesting, with the presence of a compression fracture deformity and central Schmorl’s node at the superior endplate of the lower spine (orange arrows). This focal CEP fracture is clearly evident as a disruption in the high signal band as shown on the DIR-UTE image, but is ambiguous in the clinical T_2w- and T_1w- FSE images.

Figure 4 shows representative lumbar spine images from a patient with low back pain. Similar to the case with the asymptomatic subjects, the clinical fat suppressed T_2w-FSE sequence does not capture signals from the CEP region, while the DIR-UTE, IR-FS-UTE, and T_1w-FS-UTE images present better CEP contrast than regular FS-UTE. The NP regions of degenerated discs in the DIR-UTE, IR-FS-UTE, and T_1w-FS-UTE images show relatively higher signals than those in normal discs. This may be because of shortened T₁ relaxation time in the NP due to disc dehydration [8, 30, 31].

Figure 5 shows UTE imaging of a patient with psoriatic arthritis (PsA). This patient has features of chronic inflammatory arthritis, including a Romanus lesion at the anterosuperior L2 vertebral body with erosion (shown in PDw-UTE bone image) and fatty change (shown in clinical T_1w-FSE image). Numerous bony endplate irregularities as marked by arrows are associated with the signal loss in CEP regions seen vividly in the coronal DIR-UTE image (Fig. 5C). In comparison, continuous CEP signals can be seen in the coronal DIR-UTE image from a asymptomatic subject (Fig. 5D).

Figure 6 presents DIR-UTE imaging of another patient with PsA. The L2-L4 levels show bony endplate remodeling on the PDw-UTE bone image. The CEP irregularities can be clearly seen in the corresponding DIR-UTE image at the inferior endplates of these discs (arrows). In comparison, the clinical sequences do not provide such information on CEP changes.

In this work, we have shown that the DIR-UTE sequence can provide high contrast imaging of the CEP region in both ex vivo and in vivo spine studies. Usage of two narrow-band AFP pulses in the DIR-UTE sequence can efficiently suppress long T₂ water and fat simultaneously. Moreover, the CEP region can be imaged with high contrast over a wide range of TIs in the DIR-UTE, which indicates the robustness of the proposed technique. In addition, the DIR-UTE sequence highlights the CEP with significant improvements in comparison to IR-FS-UTE, T_1w-FS-UTE, and FS-UTE sequences. Ex vivo imaging on a spine sample revealed a compression fracture that was clearly discernible by the DIR-UTE sequence. In vivo study on various asymptomatic and symptomatic subjects has confirmed that DIR-UTE sequence can capture CEP signal with high contrast and can detect abnormalities such as CEP irregularities and focal defects.

The proposed 3D DIR-UTE sequence provides better CEP contrast in comparison to previously reported dual-echo subtraction UTE and IR-FS-UTE studies, especially with regard to the contrast between the CEP and BMF [19, 32, 33]. To the best of our knowledge, this is the first in vivo CEP imaging study that uses the 3D DIR-UTE Cones technique; other studies have been focused on the T₂ * quantification of CEP using multi-echo UTE sequences [14, 34, 35]. Our study has demonstrated that this technique has great potential for morphological evaluation of the CEP and IVD health in vivo. The DIR-UTE technique incorporated with multiple-echo acquisition also allows for quantitative evaluation of CEP degeneration or calcification, which could be a new direction for future investigations.

The CEP region is an important facilitator in both biomechanical and nutritional functions of the spine. Given that the CEP is regularly subjected to significant loads during daily activities in order to stabilize spinal posture [36], end plate disruptions are likely to disrupt the uniformity of disc stress distributions [37]. This in turn accelerates matrix degradation in the CEP thereby causing the impediment of nutrient transport to the cells [38]. This phenomenon can be interpreted as the initial stages of disc degeneration and would be highly significant as a marker observable via noninvasive imaging techniques [5]. Given that conventional MRI sequences fail to capture sufficient signals from the CEP region, devising and developing novel high contrast imaging sequences, such as the DIR-UTE presented in this study, are of acute importance.

The IR preparation is much more efficient in signal suppression for the desired tissues with long T₂ relaxations than T₁ weighting (as used in the T_1w-FS-UTE sequence) is, with regard to short T₂ imaging. Moreover, since the CEP and BMF both have relatively short T₁ values, it is difficult to distinguish the regions using the T_1w-FS-UTE sequence when fat suppression is not complete. In addition, the effectiveness of the FatSat module is limited up to a certain level in the IR-FS-UTE and T_1w-FS-UTE imaging. When more spokes are utilized to speed up the imaging acquisition, the effectiveness of fat suppression for the FatSat module diminishes, resulting in a trade-off between scan efficiency and fat suppression. This fat suppression inefficiency can be avoided by replacing the FatSat module with another AFP pulse dedicated specifically to fat suppression by centering the frequency on fat.

The DIR-UTE sequence is able to detect and highlight CEP signals, allowing for more accurate morphological evaluation of CEP health in comparison to clinical MRI. For example, calcification and ossification of the CEP cannot be assessed by clinical MRI because these conditions show a similar dark appearance as normal CEP. In comparison, the DIR-UTE may be able to differentiate normal CEP from calcified and ossified CEPs due to the differences in proton density. In addition to morphological assessment of CEP health, the DIR-UTE with multiple-echo acquisition allows quantitative evaluation (i.e., T₂* measurement) of CEP biochemistry which clinical MRI cannot. Thus the DIR-UTE technique has the potential to provide more useful information than clinical MRI in the assessment of CEP and IVD health.

However, the DIR-UTE imaging could be affected by artifacts brought on by the signal fluctuations among various acquisition spokes if there is a significant increase in the number of spokes employed in one TR. For the current study, the number of spokes (N_sp = 27) was found to provide a high CNR without significant artifacts being introduced. A range of 15 to 30 for N_sp is recommended in terms of scan time and image quality.

There are several limitations in this study. First, histology was not performed to validate the signal changes of 3D DIR‐UTE imaging. Second, the spatial resolution (e.g., voxel size = 0.875 × 0.875 × 3.6mm³) was still a limiting factor for thin CEP imaging considering the signal-to-noise ratio performance of the RF coils and MRI scanners currently available, despite the high CEP contrast in the 3D DIR-UTE imaging. Third, the scan time of 10 min is relatively long in the context of a clinical setting and should be improved with parallel imaging and compressed sensing [39‐41]. Fourth, the DIR-UTE sequence is sensitive to background magnetic field inhomogeneity due to narrow bandwidth of the AFP pulses and limited chemical shift of fat at 3T. A high order shimming hardware system could potentially help for uniform signal suppression. Fifth, a relatively small number of subjects were scanned in this study. A future large cohort study will be very useful for exploring the potential of the DIR-UTE technique in clinical use. Sixth, in this study, only the DIR-UTE technique was applied for the patient scans to shorten the total scan time since these patients cannot bear a very long scan due to their moderate low back pain. The comparison of CEP contrast between all the UTE techniques for patient study will be interesting once the scan time of these UTE scans is accelerated.

In conclusion, we showed that 3D DIR-UTE sequence can be used for high contrast CEP imaging both ex vivo and in vivo. The optimized 3D DIR-UTE sequence also showed better CEP contrast than other UTE techniques, including the IR-FS-UTE, T_1w-FS-UTE, and FS-UTE sequences, suggesting that the DIR-UTE sequence may facilitate better evaluation of the vital CEP region in clinical practice.