Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2021 Aug 1.
Published in final edited form as: NMR Biomed. 2020 May 19;33(8):e4322. doi: 10.1002/nbm.4322

Magic angle effect on adiabatic T1ρ imaging of the Achilles tendon using 3D ultrashort echo time cones trajectory

Mei Wu 1,2, Yajun Ma 2, Lidi Wan 2, Saeed Jerban 2, Hyungseok Jang 2, Eric Y Chang 3,2, Jiang Du 2
PMCID: PMC7393640  NIHMSID: NIHMS1597621  PMID: 32431025

Abstract

The protons in collagen-rich musculoskeletal (MSK) tissues such as the Achilles tendon are subject to strong dipolar interactions which are modulated by the term (3cos2θ−1) where θ is the angle between the fiber orientation and the static magnetic field B0. The purpose of this study was to investigate the magic angle effect in three-dimensional ultrashort echo time Cones Adiabatic T1ρ (3D UTE Cones-AdiabT1ρ) imaging of the Achilles tendon using a clinical 3T scanner. The magic angle effect was investigated by Cones-AdiabT1ρ imaging of five cadaveric human Achilles tendon samples at five angular orientations ranging from 0° to 90° relative to the B0 field. Conventional Cones continuous wave T1ρ (Cones-CW-T1ρ) and Cones T2* (Cones-T2*) sequences were also applied for comparison. On average, Cones-AdiabT1ρ increased 3.6-fold from 13.6 ± 1.5 ms at 0° to 48.4 ± 5.4 ms at 55°, Cones-CW-T1ρ increased 6.1-fold from 7.0 ± 1.1 ms at 0° to 42.6 ± 5.2 ms at 55°, and Cones-T2* increased 12.3-fold from 2.9 ± 0.5 ms at 0° to 35.8 ± 6.4 ms at 55°. Although Cones-AdiabT1ρ is still subject to significant angular dependence, it shows a much-reduced magic angle effect compared to Cones-CW-T1ρ and Cones-T2*, and may be used as a novel and potentially more effective approach for quantitative evaluation of the Achilles tendon and other MSK tissues.

Keywords: ultrashort echo time, magic angle, AdiabT1ρ, CW-T1ρ, T2*, Achilles tendon, MSK, quantitative evaluation

Graphical Abstract

3D UTE Cones-AdiabT1ρ shows a much-reduced magic angle effect compared to 3D UTE Cones-CW-T1ρ and 3D UTE Cones-T2*, Cones-AdiabT1ρ increased 3.6-fold from 13.6 ± 1.5 ms at 0° to 48.4 ± 5.4 ms at 55°, Cones-CW-T1ρ increased 6.1-fold from 7.0 ± 1.1 ms at 0° to 42.6 ± 5.2 ms at 55°, and Cones-T2* increased 12.3-fold from 2.9 ± 0.5 ms at 0° to 35.8 ± 6.4 ms at 55°. 3D UTE Cones-AdiabT1ρ may be used as a novel and potentially more effective approach for quantitative evaluation of the Achilles tendon and other MSK tissues.

Introduction

A major confounding factor in quantitative magnetic resonance imaging of the musculoskeletal (MSK) tissues is the magic angle effect (1–7). The ordered collagen fibers in MSK tissues are subject to dipole-dipole interactions that are modulated by the term 3cos2(θ)-1, where θ is the angle between the fiber orientation and the main magnetic field B0. Two of the most widely investigated biomarkers for MSK imaging are T2 and continuous wave T1ρ (CW-T1ρ) imaging; however, both biomarkers are significantly limited by the strong magic angle effect, demonstrating up to several-fold increase in T2 and T1ρ values when θ is changed from 0° to 55° (6–7). Those increases in value can far exceed the changes caused by degeneration (8), thereby complicating diagnosis and treatment monitoring.

In recent years, researchers have tried to resolve this challenge by employing trains of adiabatic full passage (AFP) pulses to generate adiabatic T1ρ (AdiabT1ρ) relaxation (9–15). A number of experimental studies have demonstrated that AdiabT1ρ is less sensitive to the magic angle effect compared with both CW-T1ρ and T2 relaxations in bovine cartilage samples (13, 14). Furthermore, AdiabT1ρ has been shown to be sensitive to early degenerative changes in both animal and human specimens (16–18). However, AdiabT1ρ based on conventional data acquisition cannot evaluate many MSK tissues or tissue components including the deep cartilage, menisci, ligaments, tendons, and subchondral bone, which have very short T2 and are “invisible” with conventional MR sequences (19). Ultrashort echo time (UTE) sequences can be used for high resolution morphological imaging of tissues or tissue components with short transverse relaxation times (20). More recently, the combination of 3D UTE Cones data acquisition and adiabatic T1ρ preparation (3D UTE Cones-AdiabT1ρ) has been proposed for potentially magic angle-insensitive imaging of both short and long T2 tissues or tissue components in the MSK system (21). Preliminary studies of patellar cartilage show a much reduced magic angle effect as compared to CW-T1p and T2 *(22).

However, it is still unclear to what degree the 3D UTE Cones-AdiabT1ρ sequence is subject to the magic angle effect. The Achilles tendon has a highly organized collagen structure and relatively low hydration, and is known to be sensitive to the magic angle effect. Previous studies have demonstrated near 8-fold increase in UTE-T2* values and near 7-fold increase in UTE CW-T1ρ values when the Achilles tendon is oriented from 0° to 55° relative to the main magnetic field (5, 6). It is important to understand the magic angle effect in the worst-case scenario in 3D UTE Cones-AdiabT1ρ imaging of the Achilles tendon.

In this study, we applied the 3D UTE Cones-AdiabT1ρ sequence for T1ρ assessment of the Achilles tendon on a clinical 3T scanner. The magic angle effect was investigated by 3D UTE Cones-AdiabT1ρ imaging of five human Achilles tendon samples at five angular orientations ranging from 0° to 90° relative to the B0 field. Conventional 3D UTE Cones-CW-T1ρ and Cones-T2* sequences were also applied for comparison.

Methods

Human Achilles tendon samples procurement

Five cadaveric human Achilles tendon samples were harvested from freshly frozen ankle specimens (five donors aged 28–84 years, mean age 60.4±27.2 years; two males, three females) provided by a non-profit whole-body donation company (United Tissue Network, Phoenix, AZ). Achilles tendon samples of ~40mm length were cut using a Delta ShopMaster band saw (Delta Machinery, Tennessee, USA). All tendon samples were immersed in phosphate-buffered saline (PBS) for four hours at room temperature for rehydration. During MRI scanning, the tendon samples were placed in a plastic dish filled with Fomblin (Fomblin, Ausimont, Thorofare, NJ) to minimize dehydration and susceptibility artifacts at air-tissue interfaces.

MR data acquisition

The 3D UTE Cones-AdiabT1ρ sequence was implemented on a 3T MR750 whole-body scanner (GE Healthcare Technologies, Milwaukee, WI). A transmit/receive wrist coil (BC-10, Medspira, Minneapolis, MN) was used for signal excitation and reception. The 3D UTE Cones-AdiabT1ρ sequence employed an even number of adiabatic inversion recovery (NIR) pulses (Silver-Hoult fast passage inversion pulse, duration = 6.048 ms, peak power = 17 μT) followed by a regular 3D UTE Cones data acquisition (21, 23). Following each adiabatic T1ρ preparation, fast Cones data acquisition was performed using a number of spokes (Nsp) with an equal time interval τ. The spin lock time (TSL) is defined as the total duration of the train of adiabatic IR pulses, i.e. TSL=NIR×Tp (Tp is duration of a single adiabatic IR pulse). Accurate T1 measurement is needed for T1ρ calculation because of the use of a relatively short TR. 3D UTE-Cones actual flip angle imaging (AFI) was used for mapping of B1 inhomogeneity, which, together with a variable flip angle (VFA) method (3D UTE-Cones AFI-VFA), was used for accurate T1 mapping (24, 25). Features of the sequences used in this study are shown in Figure 1.

Figure 1.

Figure 1.

Open in a new tab

Quantitative 3D UTE Cones sequences include the basic 3D UTE Cones sequence (A), which employs a short rectangular pulse for signal excitation followed by 3D spiral sampling with a minimal nominal TE of 32 μs and conical view ordering (B), the 3D UTE Cones Actual flip angle imaging (AFI) sequence with dual-TR acquisitions for B1 mapping (C), the conventional 3D UTE Cones sequence with a single TR for T1 measurement with the variable flip angle (VFA) or variable repetition time (VTR) method (D), and the 3D UTE Cones-AdiabT1ρ sequences for AdiabT1ρ measurement. To speed up data acquisition, multiple spokes (Nsp) were sampled after adiabatic T1ρ preparation.

Typical imaging parameters included a field of view (FOV) of 8×8 cm2, a slice thickness of 4 mm, and a receiver bandwidth (BW) of 125 kHz. Other sequence parameters were: 1) Cones-AFI (24): TR1/TR2 = 20/100 ms, flip angle (FA) = 45°, acquisition matrix = 140×140×10, scan time = 3 min 30 sec; 2) Cones-VFA (25): TR = 20 ms, FA = 4°, 7°, 10°, 15°, 20°, 25°, and 30°; acquisition matrix = 140×140×20, scan time = 15 min 10 sec; 3) Cones-AdiabT1ρ (21): TR = 400 ms, FA = 10°, acquisition matrix = 140×140×20, Nsp = 11, NIR = 0, 2, 4, 6, 8, 12, 16, and 20, each with a scan time of 4 min; 4) Cones-CW-T1ρ (26): TR = 400 ms, FA = 10°, acquisition matrix = 140×140×20, Nsp = 11, TSL = 0, 1, 3, 6, 10, and 15 ms, each with a scan time of 4 min; 5) Cones-T2*: TR = 50 ms, FA = 15°, acquisition matrix = 140×140×20, fat saturation, three sets of dual-echo acquisitions (TEs = 0.032/8.8, 2.2/14, and 4.4/20 ms) with a scan time of 13 min 45 sec. Clinical T1- and T2-weighted fast spin echo (FSE) sequences were also performed with similar spatial resolution for confirmation of specimen abnormality and determination of specimen rotation. The imaging protocol was repeated five times, each with a different orientation (0°, 30°, 55°, 70°, and 90° relative to B0). The rotating scheme is shown in Figure 2.

Figure 2.

Figure 2.

Open in a new tab

The rotating scheme in the magic angle study of cadaveric human Achilles tendon samples. Achilles tendon samples were rotated 0°, 30°, 55°, 70°, and 90° relative to the B0 field.

Image analysis

All 3D UTE Cones datasets, including Cones-AFI, Cones-VFA, Cones-AdiabT1ρ, Cones-CW-T1ρ, and Cones-T2* acquired at five different angular orientations were first manually aligned using ImageJ software, then automatically registered with FLIRT (Functional MRI of the Brain’s Linear Image Registration Tool) software using six parameter rigid body model and correlation ratio as the cost function (27). The DICOM images obtained by the acquisition protocols described above were analyzed with MATLAB 2017 (The MathWorks, Natick, MA). Two radiologists drew different regions of interest (ROIs) on three slices images of each Achilles tendon sample. ROIs were drawn in the central portion of the Achilles tendon, avoiding fat and bubbles. The home-developed MATLAB program allowed copying and pasting of ROIs to the registered images, as that ROIs were identically located on images obtained at different angles and sequences. Single-component model was applied to fit T1, Cones-CW-T1ρ, Cones-AdiabT1ρ, and Cones-T2*. The angular dependence of each biomarker was analyzed. Intraclass correlation efficient (ICC) was used to evaluate consistency between the two radiologists.

Results

All samples were visually normal, which was further confirmed by clinical MR sequences. Figure 3 shows representative images from 3D UTE Cones-AdiabT1ρ imaging, regular Cones CW-T1ρ imaging, and Cones-T2* imaging of the same Achilles tendon sample oriented 0° and 55° relative to the B0 field, respectively. Signal from the Achilles tendon decayed much faster at 0° than at 55° when scanned using regular 3D UTE Cones-CW-T1ρ and Cones-T2* sequences. In comparison, the 3D UTE Cones-AdiabT1ρ images show reduced signal differences at 0° than 55°.

Figure 3.

Figure 3.

Open in a new tab

3D UTE Cones-AdiabT1ρ imaging of an Achilles tendon sample oriented 0° (A-D) and 55° (a-d) relative to the B0 field with a series of TSLs of 0 ms (A, a), 24 ms (B, b), 48 ms (C, c), and 72 ms (D, d). Regular 3D UTE-Cones CW-T1ρ imaging of the same Achilles tendon sample oriented 0° (E-H) and 55° (e-h) relative to the B0 field with a series of TSLs of 0 ms (E, e), 6 ms (F, f), 10 ms (G, g), and 15 ms (H, h). 3D UTE Cones-T2* imaging of the same Achilles tendon sample oriented 0° (I-L) and 55° (i-l) relative to the B0 field with a series of TEs of 0 ms (I, i), 4.4 ms (J, j), 8.8 ms (K, k), and 14 ms (L, l). Signal for the Achilles tendon acquired by 3D UTE-Cones-AdiabT1ρ imaging decays much slower at 0° than that acquired by the latter two sequences.

Figure 4 shows exponential fitting curves for a global ROI of an Achilles tendon sample oriented 0°, 30°, 55°, 70°, and 90° to the B0 field using 3D UTE Cones-AdiabT1ρ, regular Cones-CW-T1ρ, and Cones-T2* imaging, respectively. Cones-AdiabT1ρ values show the smallest magic angle effect with a 3.5-fold increase through the minimization of dipolar interaction at 55°. In comparison, Cones-CW-T1ρ and Cones-T2* showed much stronger magic angle effects with 5.3-fold and 13.8-fold increases, respectively.

Figure 4.

Figure 4.

Open in a new tab

Exponential fitting curves for a global ROI of an Achilles tendon sample oriented 0°, 30°, 55°, 70°, and 90° to the B0 field using 3D UTE-Cones-AdiabT1ρ imaging (A-E), regular 3D UTE Cones-CW-T1ρ imaging (F-J), and 3D UTE Cones-T2* imaging (K-O). Cones-AdiabT1ρ values show the smallest magic angle effect with 3.5-fold increase from 13.9 ms at 0° to 48.7 ms at 55°. Regular Cones-CW-T1ρ values show increased magic angle effect with a 5.3-fold increase from 7.8 ms at 0° to 41.0 ms at 55°. Cones-T2*values show the largest magic angle effect with a 13.8-fold increase from 2.3 ms at 0° to 31.7 ms at 55°.

Figure 5 shows the angular dependence of 3D UTE Cones-AdiabT1ρ, Cones-CW-T1ρ, and Cones-T2* for a representative human Achilles tendon sample. Cones-AdiabT1ρ shows a much reduced magic angle effect as compared to Cones-CW-T1ρ (3.7-fold reduction) and Cones-T2* values (6.6-fold reduction).

Figure 5.

Figure 5.

Open in a new tab

The angular dependence of 3D UTE Cones-AdiabT1ρ (A), regular 3D UTE Cones-CW-T1ρ (B), and 3D UTE Cones-T2* (C), as well as the fold changes of all three biomarkers (D) for a human Achilles tendon sample. The mean and standard deviation for Cones-AdiabT1ρ, Cones-CW-T1ρ, and Cones-T2* values at 0°, 30°, 55°, 70°, and 90° relative to the B0 field are displayed. The Cones-AdiabT1ρ values show the least angular dependence with 3.3-fold increase from 0° to 55°. The Cones-CW-T1ρ and Cones-T2* values increased by 7.0-fold and 9.9-fold, respectively.

Table 1 summarizes the mean 3D UTE Cones-AdiabT1ρ, Cones-CW-T1ρ, and Cones-T2* values of the Achilles tendon from five human cadaveric ankle specimens. Excellent inter-observer agreement was achieved between the two radiologists in quantitative analysis (ICC=0.950–0.997, p<0.001). Cones-AdiabT1ρ shows the smallest magic angle effect, with 3.6-fold increase from 13.6 ms at 0° to 48.4 ms at 55°. Cones-CW-T1ρ shows much increased magic angle effect, with 6.1-fold increase from 7.0 ms at 0° to 42.6 ms at 55° (Supporting Table S1), while Cones-T2* shows the strongest magic angle effect, with 12.3-fold increase from 2.9 ms at 0° to 35.8 ms at 55° (Supporting Table S2).

Table 1.

Average 3D UTE Cones-AdiabT1ρ relaxation times of five Achilles tendon samples measured with the Achilles tendon oriented 0°, 30°, 55°, 70°, and 90° relative to the B0 field.

sample T1ρ at 0° (ms) T1ρ at 30° (ms) T1ρ at 55° (ms) T1ρ at 70° (ms) T1ρ at 90° (ms)
1 15.6 ± 0.7 26.7 ± 1.4 56.8 ± 5.8 41.8 ± 3.1 30.2 ±1.4
2 13.9 ± 0.7 22.9 ± 1.2 48.7 ± 4.9 35.3 ± 2.5 29.3 ± 1.6
3 12.4 ± 0.5 21.7 ± 1.0 48.0 ± 5.1 35.7 ± 2.8 27.5 ± 1.6
4 11.8 ± 0.3 19.5 ± 0.8 41.8 ± 4.0 35.1 ± 2.9 27.4 ± 1.5
5 14.2 ± 0.5 22.9 ± 1.1 46.7 ± 4.6 39.7 ± 3.4 32.0 ± 2.0
Average 13.6 ± 1.5 22.7 ± 2.6 48.4 ± 5.4 37.5 ± 3.0 29.3 ± 1.9
Open in a new tab

Discussion

Although several research studies have focused on quantitative magnetic resonance imaging of MSK tissues, there are still very limited clinical applications in the assessment of knee joint degeneration and other MSK diseases (28). As mentioned, one of the major problems is the strong magic angle effect in most current MRI biomarkers, including T2, T2* and CW-T1ρ (1–7). While it is generally accepted that tissue degeneration is associated with an increase in T2, T2*, and/or T1ρ, the strong orientation dependence may make numeric interpretation of those biomarkers difficult or impossible. The less orientation-dependent AdiabT1ρ is expected to contain more information on the degeneration of the Achilles tendon than the more orientation-dependent T2, T2* or CW-T1ρ. Another major limitation is the incapability of conventional MR sequences in quantitative evaluation of short T2 tissues, which are broadly involved in various MSK diseases, but are generally inaccessible due to little or low signal when imaged using clinical MRI with too long echo times (19, 20, 29, 30). The 3D UTE sequence nicely resolves this limitation by providing high signal from those short T2 tissues, allowing morphological and quantitative assessment of tissue properties including their T2, T2* and T1ρ relaxation times.

The combination of a 3D ultrashort echo time sequence, a Cones trajectory, and an adiabatic T1ρ preparation seems to have potential for resolving these challenges. First, the 3D UTE sequence allows signal detection from short T2 tissues which are “invisible” with conventional clinical sequences. The UTE sequences have been applied to the Achilles tendon and enthesis, generating signals far higher than those produced by clinical sequences (5). Second, the Cones trajectory is highly efficient in covering 3D k-space, allowing fast volumetric imaging of short T2 tissues (23). Volumetric imaging of both short and long T2 tissues in the knee and ankle joints can be achieved in a few minutes with high spatial resolution and broad coverage, facilitating clinical application. Third, the adiabatic T1ρ preparation allows quantitative T1ρ imaging with much reduced angular dependence (9–15). This feature has been demonstrated by several prior studies where AdiabT1ρ shows much reduced magic angle effect compared with CW-T1ρ and T2 relaxation times (13, 14). The mean effective spin locking field in the AdiabT1ρ measurement was stronger than that in the conventional T1ρ scan (AdiabT1ρ was longer than CW-T1ρ). The spectral bandwidth of the adiabatic pulse is also much broader than that of the CW spin-locking pulse. The stronger spin locking field together with the broader spectral bandwidth efficiently suppress not only the effect of orientation-dependent residual dipolar coupling, but also the chemical exchange-related relaxation contributions, namely the contribution of the proton exchange with OH groups of proteoglycans (9–18).

However, it is important to understand the capability and limitation of the 3D UTE Cones-AdiabT1ρ sequence in quantitative imaging of MSK tissues. The Achilles tendon has a highly organized collagen structure and is ideal for this kind of study (1). Our magic angle study using human Achilles tendon samples suggests that 3D UTE Cones-AdiabT1ρ is still subject to significant magic angle effect. However, it is indeed much less sensitive to the magic angle effect than both Cones-CW-T1ρ and Cones-T2*. Figure 3 shows that signals generated by regular 3D UTE Cones-CW-T1ρ imaging and Cones-T2* imaging decay much faster at 0° compared to 55°. Figures 4 and 5 show that both Cones-CW-T1ρ and Cones-T2* are peaked at an angular orientation of 55°, with approximately 5–7-fold and 10–14-fold higher relaxation times than those near 0°. Meanwhile, Cones-AdiabT1ρ shows the least angular dependence with around 3-fold increase from 0° to 55°. Table 1 summarizes the mean Cones-AdiabT1ρ values of the Achilles tendon at all five angular orientations. Cones-AdiabT1ρ has the smallest magic angle dependence, with an average 3.6-fold increase from 0° to 55°, which is much smaller than the 6.1-fold increase for Cones-CW-T1ρ and 12.3-fold increase for Cones-T2*. These results suggest that the dipole–dipole interaction makes a dominant contribution to Cones-CW-T1ρ, Cones-T2*, and Cones-AdiabT1ρ relaxations in the Achilles tendon. However, Cones-AdiabT1ρ is much less sensitive to the magic angle effect than Cones-CW-T1ρ and Cones-T2*.

Cones-AdiabT1ρ may have advantages over Cones-CW-T1ρ, Cones-T2*, and CPMG-T2 in assessing many musculoskeletal tissues such as the articular cartilage, menisci, ligaments, tendons, muscle, etc. The Achilles tendon has a more organized collagen fiber structure than many other MSK tissues (1) and is therefore expected to be subject to a greater magic angle effect. The 3.6-fold increase in AdiabT1ρ from 0° to 55° is likely the worst-case scenario in the magic angle effect for all MSK tissues. Other MSK tissues, such as the articular cartilage, have a more complicated collagen network structure and the magic angle effect is likely to be averaged. Indeed, our recent studies suggest a greatly reduced magic angle effect in 3D UTE Cones-AdiabT1ρ imaging of patella samples, where 3D UTE Cones-AdiabT1ρ showed 25.7% increase while Cones-CW-T1ρ and Cones-T2* showed 89.5% and 203.5% increase when the patella samples were oriented from 0° to 55° relative to the B0 field (22). This is very promising data, suggesting that 3D UTE Cones-AdiabT1ρ imaging may be used for magic angle-insensitive evaluation of proteoglycan (PG) depletion in articular cartilage, thus facilitating early diagnosis of osteoarthritis (OA). Our previous study has also shown that the proposed 3D UTE Cones-AdiabT1ρ sequence can provide reliable volumetric T1ρ assessment of both short and long T2 tissues in whole knee imaging on a clinical 3T scanner (21). The protocol can be easily applied to healthy volunteers and OA patients for clinical evaluation.

It is noteworthy to mention that both UTE T1ρ and T2* have clinical values although they are sensitive to the magic angle effect. A series of recent studies suggest that degenerated tendons have increased T1ρ and T2* values. Qiao et al. compared UTE T2* values of healthy and diseased Achilles tendons and found strong correlations between T2* and the American Orthopaedic Foot and Angle Society (AOFAS) score (r = −0.733) and the Achilles Tendon Rupture Score (ATRS) (r = −0.634) (31). Kijowski et al. performed bi-component UTE T2* analysis for assessment of patients with patellar tendinopathy, and found that abnormal patellar tendon had significantly longer short T2*s (1.3 ms vs. 1.5 ms) and lower short T2* fraction (75.5% vs. 79.5%) (32). Koff et al. employed UTE for imaging of cyclically loaded rabbit patellar tendon, and found significantly shorter T2* values after cyclic loading (33). Jerban et al. reported significant UTE T2* reduction in tendons with application of static tensile loads (34). As the 3D UTE Cones-AdiabT1ρ sequence is less sensitive to the magic angle effect, it is expected that Cones-AdiabT1ρ may be more sensitive to tendon degeneration, as well as the reduction in mechanical properties due to overuse or disease-related degeneration.

In addition, Cones-AdiabT1ρ has other advantages. First, adiabatic pulses are less sensitive to the spatial inhomogeneity of the transmit RF magnetic field. This is a significant advantage over the conventional continuous wave T1ρ, where RF inhomogeneity introduces significant errors if not fully compensated for. Second, the AFP pulse is flexible and can therefore moderate the RF power deposition (9–15), greatly reducing the effective specific absorption ratio (SAR). Third, significant scan time reduction can be achieved for the 3D UTE Cones-AdiabT1ρ sequence by using multi-spoke data acquisition (21). With a number of spokes (Nsp) acquired after each adiabatic preparation, the scan time is reduced by a factor of Nsp. Our simulation study suggests that accurate Cones-AdiabT1ρ can be achieved with Nsp up to 40 or higher (21). Fourth, our recent studies have shown that extended Cones sampling can be used to speed up data acquisition without significant comprising quantitative assessment of tissue properties (35). This sampling strategy may also be combined with 3D UTE Cones-AdiabT1ρ imaging for fast volumetric Cones-AdiabT1ρ mapping. Fifth, an extended range of frequencies or correlation times may provide more information on the physicochemical mechanisms underlying pathological changes in tissues (12), although further research is still required regarding mechanisms about the reduced magic angle sensitivity with Cones-AdiabT1ρ.

There are several limitations of this study. First, the number of samples is small, with only five cadaveric human Achilles tendon samples from five different donors. We chose three different slices and two different ROIs in each slice of each sample to increase our analysis statistics. Second, only Achilles tendon samples were used for this magic angle study. Other tissues, such as articular cartilage, menisci, and ligaments were not investigated. It is believed that results from this study represent the worst-case scenario, as the Achilles tendon has a more organized collagen fiber structure and is subject to stronger magic angle effect. Third, the scan time of 3D UTE Cones-AdiabT1ρ sequence was relatively long (~15 min) and is not suitable for patient examination. The long scan time is associated with the high spatial resolution, broad slice coverage with a large number of slices, and many TSLs required for more accurate quantification of Cones-AdiabT1ρ for the Achilles tendon specimens. Lower spatial resolution together with a smaller number of TSLs can be used to further reduce the total scan time, facilitating clinical applications. Fourth, we used a single component model, but tendons may have more than one relaxation component; a bi-component model with two distinct water compartments may allow more accurate evaluation of the AdiabT1ρ relaxation (36), which clearly requires further investigation. Fifth, the sensitivity of Cones-AdiabT1ρ to tissue degeneration is not investigated in this study. There are contradicting results regarding the correlation between T1ρ and PG depletion. While some studies demonstrated a negligible effect of PG concentration on T1ρ (37–39), other studies demonstrated a high linear increase in T1ρ with PG depletion (40–42). The investigation of the relationship between Cones-AdiabT1ρ and PG depletion is of critical importance.

Conclusion

The 3D UTE Cones-AdiabT1ρ biomarker shows much reduced magic angle effect in imaging the Achilles tendon as compared to Cones-CW-T1ρ and Cones-T2*. The 3D UTE Cones-AdiabT1ρ sequence may be used as a novel and potentially more effective approach for more accurate quantification of the Achilles tendon and other short T2 tissues in the MSK systems.

Supplementary Material

supp info

Table S1. Average 3D UTE Cones-CW-T1ρ relaxation times of five Achilles tendon samples measured with the Achilles tendon oriented 0°, 30°, 55°, 70°, and 90° relative to the B0 field.

Table S2. Average 3D UTE Cones-T2* relaxation times of five Achilles tendon samples measured with the Achilles tendon oriented 0°, 30°, 55°, 70°, and 90° relative to the B0 field.

Acknowledgements

The authors acknowledge grant support from NIH (2R01AR062581, 1R01AR075825, and 1R01NS092650) and the VA (I01RX002604 and I01RX001388).

Abbreviations

AdiabT1ρ

adiabatic T1ρ

AFI

actual flip angle

AFP

adiabatic full passage

BW

receiver bandwidth

Cones-AdiabT1ρ

Cones Adiabatic T1ρ

Cones-CW-T1ρ

Cones continuous wave T1ρ

Cones-T2*

Cones T2*

CW-T1ρ

continuous wave T1ρ

FA

flip angle

FOV

field of view

MSK

musculoskeletal

NIR

number of inversion recovery

Nsp

number of spokes

OA

osteoarthritis

PBS

phosphate-buffered saline

PG

proteoglycan

ROI

region of interest

SAR

specific absorption ratio

3D

Three-dimensional

TSL

spin locking time

UTE

ultrashort echo time

VFA

variable flip angles

References

  • 1.Fullerton GD, Cameron IL, Ord VA. Orientation of tendons in the magnetic field and its effect on T2 relaxation time. Radiology 1985; 155:433–435. [DOI] [PubMed] [Google Scholar]
  • 2.Henkelman RM, Staniz GJ, Kim JK, Bronskill MJ. Anisotropy of NMR properties of tissues. Magn Reson Med 1994; 32:592–601. [DOI] [PubMed] [Google Scholar]
  • 3.Mlynarik V, Szomolanyi P, Toffanin R, Vittur F, Trattnig S. Transverse relaxation mechanisms in articular cartilage. J Magn Reson 2004; 300–307. [DOI] [PubMed] [Google Scholar]
  • 4.Mlynarik V, Trattnig S, Huber M, Zembsch A, Imhof H. The role of relaxation times in monitoring proteoglycan depletion in articular cartilage. J Magn Reson Imaging 1999; 10:497–502. [DOI] [PubMed] [Google Scholar]
  • 5.Du J, Pak BC, Znamirowski R, Statum S, Takahashi A, Chung CB, Bydder GM. Magic Angle Effect in Magnetic Resonance Imaging of the Achilles Tendon and Enthesis. Magn Reson Imaging 2009; 27:557–564. [DOI] [PubMed] [Google Scholar]
  • 6.Du J, Statum S, Znamirowski R, Bydder GM, Chung CB. Ultrashort TE T1ρ magic angle imaging. Magn Reson Med. 2013; 69(3): 682–687. [DOI] [PubMed] [Google Scholar]
  • 7.Shao H, Pauli C, Li S, Ma Y, Tadros AS, Kavanaugh A, Chang EY, Tang G, Du J. Magic angle effect plays a significant role in T1rho relaxation in articular cartilage. Osteoarthritis Cartilage 2017; 25:2022–2030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Mosher TJ, Zhang Z, Reddy R, Boudhar S, Milestone BN, Morrison WB, Kwoh CK, Eckstein F, Witschey WR, Borthakur A. Knee articular cartilage damage in osteoarthritis: analysis of MR image biomarker reproducibility in ACRIN-PA 4001 multicenter trial. Radiology 2011; 258:832–842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Garwood M, DelaBarre L. The return of the frequency sweep: designing adiabatic pulses for contemporary NMR. J Magn Reson. 2001; 153: 155–177. [DOI] [PubMed] [Google Scholar]
  • 10.Michaeli S, Grohn H, Grohn O, Sorce DJ, Kauppinen R, Springer CS Jr, Uğurbil K, Garwood M. Exchange-influenced T2rho contrast in human brain images measured with adiabatic radio frequency pulses. Magn Reson Med. 2005; 53(4): 823–829. [DOI] [PubMed] [Google Scholar]
  • 11.Michaeli S, Sorce DJ, Springer CS Jr, Ugurbil K, Garwood M. T1rho MRI contrast in the human brain: modulation of the longitudinal rotating frame relaxation shutter-speed during an adiabatic RF pulse. J Magn Reson. 2006; 181: 135–147. [DOI] [PubMed] [Google Scholar]
  • 12.Casula V, Autio J, Nissi MJ, Auerbach EJ, Ellermann J, Lammentausta E, Nieminen MT. Validation and optimization of adiabatic T1ρ and T2ρ for quantitative imaging of articular cartilage at 3 T. Magn Reson Med. 2017; 77(3): 1265–1275. [DOI] [PubMed] [Google Scholar]
  • 13.Nissi MJ, Mangia S, Michaeli S, Nieminen MT. Orientation anisotropy of rotating frame and T2 relaxation parameters in articular cartilage. In: Proceedings of the 21st Annual Meeting of ISMRM, Salt Lake City, UT, 2013. Abstract 3552. [Google Scholar]
  • 14.Hänninen N, Rautiainen J, Rieppo L, Saarakkala S, Nissi MJ. Orientation anisotropy of quantitative MRI relaxation parameters in ordered tissue. Sci Rep. 2017; 7(1): 9606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Zhang J, Nissi MJ, Idiyatullin D, Michaeli S, Garwood M, Ellermann J. Capturing fast relaxing spins with SWIFT adiabatic rotating frame spin–lattice relaxation (T1ρ) mapping. NMR Biomed. 2016; 29(4): 420–430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Rautiainen J, Nissi MJ, Liimatainen T, Herzog W, Korhonen RK, Nieminen MT. Adiabatic rotating frame relaxation of MRI reveals early cartilage degeneration in a rabbit model of anterior cruciate ligament transection. Osteoarthritic Cartilage 2014; 22:1444–1452. [DOI] [PubMed] [Google Scholar]
  • 17.Rautiainen J, Nissi MJ, Salo EN, Tiitu V, Finnila MA, Aho OM, Saarakkala S, Lehenkari P, Ellermann J, Nieminen MT. Multiparametric MRI assessment of human articular cartilage degeneration: correlation with quantitative histology and mechanical properties. Magn Reason Med 2015; 74:249–259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Nissi MJ, Salo EN, Tiitu V, Liimatainen T, Michaeli S, Mangia S, Ellermann J, Nieminen MT. Multi-parametric MRI characterization of enzymatically degraded articular cartilage. J Orthop Res 2016; 34:1111–1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Robson MD, Gatehouse PD, Bydder M, Bydder GM. Magnetic resonance: an introduction to Ultrashort TE (UTE) imaging. J Comput Assist Tomogr 2003; 27:825–846. [DOI] [PubMed] [Google Scholar]
  • 20.Chang EY, Du J, Bae WC, Chung CB. Qualitative and quantitative ultrashort echo time imaging of musculoskeletal tissues. Semin Musculoskelet Radiol. 2015; 19(4): 375–386. [DOI] [PubMed] [Google Scholar]
  • 21.Ma Y, Carl M, Searleman A, Lu X, Chang EY, Du J. Three dimensional adiabatic T1ρ prepared ultrashort echo time Cones (3D AdiabT1ρ UTE-Cones) sequence for whole knee imaging. Magn Reson Med 2018; 80(4):1429–1439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Wu M, Ma Y, Wan L, Guo T, Jerban S, Jang H, Chang EY, Du J. Assessment of the Angular Dependence of 3D Ultrashort Echo Time Cones Adiabatic T11ρ (3D UTE-Cones-AdiabT11ρ) Imaging. In: Proceedings of the 27th Annual Meeting of ISMRM, Montreal, Canada, 2019. Program #1313. [Google Scholar]
  • 23.Carl M, Bydder GM, Du J. UTE imaging with simultaneous water and fat signal suppression using a time-efficient multi-spoke inversion recovery pulse sequence. Magn Reson Med 2016; 76:577–582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Ma YJ, Lu X, Carl M, Zhu Y, Szeverenyi N, Bydder GM, Chang E, Du J. Accurate T1 mapping of short T2 tissues using a three-dimensional ultrashort echo time cones actual flip angle – variable TR (3D UTE-Cones AFI-VTR) method. Magn Reson Med. 2018; 80(2):598–608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Ma YJ, Zhao W, Wan L, Guo T, Searleman A, Jang H, Chang EY, Du J. Whole knee joint T1 values measured in vivo at 3T by combined 3D ultrashort echo time cones actual flip angle and variable flip angle methods. Magn Reson Med. 2019; 81(3):1634–1644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Ma Y, Carl M, Shao H, Tadros A, Chang EY, Du J. Three-dimensional Ultrashort Echo Time Cones T1ρ (3D UTE-Cones-T1ρ) Imaging. NMR in Biomed 2017; 30:e3709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Jenkinson M, Bannister P, Brady JM and Smith SM Improved Optimisation for the Robust and Accurate Linear Registration and Motion Correction of Brain Images. NeuroImage, 17(2), 825–841, 2002. [DOI] [PubMed] [Google Scholar]
  • 28.Eckstein F, Burstein D, Link TM. Quantitative MRI of cartilage and bone: degenerative changes in osteoarthritis. NMR Biomed 2006; 19:822–854. [DOI] [PubMed] [Google Scholar]
  • 29.Du J, Bydder M, Takahashi AM, Carl M, Chung CB, Bydder GM. Short T2 contrast with three-dimensional ultrashort echo time imaging. Magn Reson Imaging 2011; 29:470–482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Sneag DB, Shah P, Koff MF, Lim WY, Rodeo SA, Potter HG. Quantitative ultrashort echo time magnetic resonance imaging evaluation of postoperative menisci: a pilot study. HSS J 2015; 11:123–129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Qiao Y, Tao HY, Ma K, Wu ZY, Qu JX, Chen S. UTE-T2* analysis of diseased and healthy Achilles tendons and correlation with clinical score: an in vivo preliminary study. Biomed Res Int 2017; 2017:2729807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Kijowski R, Wilson JJ, Liu F. Bi-component ultra-short echo time T2* analysis for assessment of patients with patellar tendinopathy. J Magn Reason Imaging 2017; 46:1441–1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Koff MF, Pownder SL, Shah PH, Yang LW, Potter HG. Ultrashort echo imaging of cyclically loaded rabbit patellar tendon. J Biomech 2014; 47:3428–3432. [DOI] [PubMed] [Google Scholar]
  • 34.Jerban S, Nazaran A, Cheng X, Carl M, Szeverenyi N, Du J, Chang EY. Ultrashort echo time T2* values decrease in tendons with application of static tensile loads. J Biomech 2017; 61:160–167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Wan L, Zhao W, Ma Y, Jerban S, Searleman AC, Carl M, Chang EY, Tang G, Du J. Fast quantitative 3D ultrashort echo time MRI of cortical bone using extended cones sampling. Magn Reson Med 2019; 82:225–236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Sharafi A, Baboli R, Chang G, Regatte RR. 3D-T1ρ prepared zero echo time-based PETRA sequence for in vivo biexponential relaxation mapping of semisolid short-T2 tissues at 3T. J Magn Reson Imaging 2019; 50:1207–1218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Menezes NM, Gray ML, Hartke JR, Burstein D. T2 and T1ρ MRI in articular cartilage systems. Magn Reson Med 2004; 51:503–509. [DOI] [PubMed] [Google Scholar]
  • 38.Keenan KE, Besier TF, Pauly JM, Han E, Rosenberg J, Smith RL, Delp SL, Beaupre GS, Gold GE. Prediction of glycosaminoglycan content in human cartilage by age, T1ρ and T2 MRI. Osteoarthritis Cartilage 2011; 19:171–179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Pang Y An order parameter without magic angle effect (OPTIMA) derived from R1ρ dispersion in ordered tissue. Magn Reson Med 2020; 83:1783–1795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Duvvuri U, Reddy R, Patel SD, Kaufman JH, Kneeland JB, Leigh JS. T1rho-relaxation in articular cartilage: effects of enzymatic degradation. Magn Reson Med 1997; 38:863–867. [DOI] [PubMed] [Google Scholar]
  • 41.Regatte RR, Akella SV, Borthakur A, Kneeland JB, Reddy R. Proteoglycan depletion-induced changes in transverse relaxation maps of cartilage: comparison of T2 and T1rho. Acad Radiology 2002; 9:1388–1394. [DOI] [PubMed] [Google Scholar]
  • 42.Li X, Ma B, Link TM, Castillo D, Blumenkrantz G, Lozano J, Carballido-Gamio J, Ries M, Majumdar S. In vivo T1ρ and T2 mapping of articular cartilage in osteoarthritis of the knee using 3T MRI. Osteoarthritis and Cartilage 2007; 15:789–797. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

supp info

Table S1. Average 3D UTE Cones-CW-T1ρ relaxation times of five Achilles tendon samples measured with the Achilles tendon oriented 0°, 30°, 55°, 70°, and 90° relative to the B0 field.

Table S2. Average 3D UTE Cones-T2* relaxation times of five Achilles tendon samples measured with the Achilles tendon oriented 0°, 30°, 55°, 70°, and 90° relative to the B0 field.

NIHMS1597621-supplement-supp_info.docx (16.1KB, docx)

RESOURCES