Introduction

Magnetic resonance (MR) imaging is an imaging modality with good soft tissue contrast and high sensitivity for detection of pancreatic cancer, which facilitates early tumor detection [1, 2]. Modern MRI techniques can visualize biliary and pancreatic ductal systems noninvasively, have a high sensitivity for tumor detection, and, unlike endo-ultrasound imaging (EUS) with high sensitivity (up to 89%) and specificity (up to 99%) for detection of small-tumor pancreatic cancer [3,4,5], reveal the pancreatic three-dimensional anatomy, possible invasion into surrounding tissue or vascular involvement [6]. However, it is still difficult to distinguish chronic pancreatitis and pancreatic carcinoma using T1-weighted and/or T2-weighted MR images on 1.5 and 3 Tesla (T) [7], even when gadolinium contrast agents are used [8].

Higher magnetic field strengths, such as 7 T, offer higher signal-to-noise (SNR) and contrast-to-noise ratios (CNR), as well as higher spatial and spectral resolutions [9]. However, artifacts are more profound at higher field strengths, particularly in the abdominal region, mainly due to the reduced wavelength in the body that leads to an inhomogeneous B1+ field distribution and signal voids [10, 11]. In addition, the local specific absorption rate (SAR) increases with increasing field strength [12], leading to longer repetition times needed and thus longer acquisitions. Using a multi-transmit system, the B1+ efficiency can be optimized within a region of interest (ROI). This can be achieved by optimizing the transmit phases for each channel in the body coil. As a result, improved local B1+ homogeneity and magnitude can be achieved [10].

In addition to the technical challenges that MRI at higher magnetic field strengths brings, high-quality diagnostic imaging of pancreatic cancer requires development and optimization of imaging protocols. Moreover, a new baseline assessment of the images obtained at ultra-high field is required. Therefore, knowledge of relaxation times (T1 and T2) is essential. These characteristics are known to change substantially with field strength and this change cannot be predicted accurately with theoretical calculations due to the complex tissue behavior [13]. Consequently, although T1 and T2 values have been well established for many tissues, including pancreatic tissue at 1.5 T and 3 T [14,15,16], T1 and T2 relaxation times of pancreatic tissue at 7 T remain unknown.

The purpose of this study was to determine the mean T1 and T2 relaxation times of healthy pancreas parenchyma over a wide age range at 7 T to assess baseline levels to develop optimized imaging protocols at this magnetic field strength.

Materials and methods

Study population and hardware

Twenty-six healthy subjects were scanned with a 7 T MR system (Philips, Best, The Netherlands) after providing a written informed consent. A multi-transmit system with eight parallel transmit channels was used, where each channel was connected to a transmit-receive fractionated dipole antenna (MR Coils BV, Drunen, The Netherlands) [17]. Each antenna had 2 additional receive loops integrated in its housing (16 in total) and were interfaced to a 16-channel receiver box (Philips, Best, The Netherlands).

Image acquisition

All scans were acquired in a ‘feet first’ supine position, with the eight channels positioned symmetrically around the abdomen, approximately centered at the height of the pancreas. First, a gradient echo image was obtained for anatomy localization and optimization steps (2D T1 fast field echo (FFE), FA = 15°, TR/TE = 10/5 ms, FOV = 704 × 704 mm2, 0.7 × 0.7 × 10 mm3 voxels). Part of the optimization was RF phase shimming, in which the RF phase of each antenna is steered to maximize and homogenize the B1+ field in the pancreas region (ROI). An in-house developed MATLAB (©MATLAB 2015b) script was used for loading a dynamic imaging series (fast field echo (FFE), FA = 4°, TR/TE = 30/1.68 ms, 0:25 min total acquisition time, 1.1 × 1.1 × 10 mm3 voxels), drawing an ROI including the whole pancreas, and optimizing the phase of each element, while keeping a fixed power using a numerical optimization algorithm. After this, image-based B0 shimming was performed. Subsequently, a B1+ map was acquired (fast field echo (FFE), FA = 50°, TR/TE = 50–250/2.2 ms, 1:29 min total acquisition time, 1.2 × 1.2 × 10 mm3 voxels) for power optimization in the pancreas region. Finally, to guarantee optimal performance in the T2-weighted MRI protocol, the power was adjusted to reach a B1+ of 10 µT within the pancreas.

A Look-Locker sequence was used for T1 relaxation determination in one slice containing the pancreas in 22 subjects (inversion recovery turbo field echo (TFE), FA = 3°, TR/TE = 40/1.68 ms, 20 measurement times separated by 100 ms, during a 6 s cycle, 8:33 min total acquisition time, 4 × 4 × 10 mm3 voxels).

Since T2 relaxation time quantification is known to be sequence dependent [18,19,20], we used three different methods to quantify the T2 relaxation times. In the first method (1), including three subjects, separated T2-weighted images were acquired in a single slice for four different echo times to determine T2 relaxation times in the pancreas using a 2D single-shot turbo spin-echo (2D single-shot turbo spin-echo (TSE), effective TR/TE = 20 s/50; 80; 100; 150 ms, refocusing FA = 180°, mean pixel BW = 341 Hz/px, 1.5 × 1.5 × 5 mm3 voxels, FOV = 320 × 400 mm2, SAR = 1.2 W/kg, Acq. time per image = 20 s). The choice of this long effective TR was made to keep SAR within (conservative) safe limits. In the second method (2), including 4 subjects, magnetic resonance spectroscopy measurements were obtained with a stimulated echo acquisition mode (STEAM) sequence at 10 different echo times on a single voxel (Fig. 1a) placed in the pancreas (TEs = 20–110 ms, TM/TR = 1.22/1500 ms, 20 × 40 × 20 mm3 voxel, 2048 points, 4 kHz bandwidth, NSA = 4). Finally, the last method (3) was applied in the remaining subjects (16) to examine the age dependency of T2 relaxation times. This was done using a 2D single-shot turbo spin-echo acquired in a single slice separately for all different echo times with a refocusing pulse of 35° (2D single-shot turbo spin-echo (TSE), TR/TE = 10 s/ 50; 80; 100; 150 ms (TEequiv = 24; 32; 36; 46 ms), FA 90°, mean pixel BW = 329 Hz/px, 1.5 × 1.5x5 mm3 voxels, FOV = 320 × 400 mm2, SAR = 0.15 W/kg, Acq. time per image = 10 s, TSE factor varying between 115 and 157, SPAIR fat suppression), which is a robust protocol with shorter scan times and lower SAR levels ( ~ 85% lower) when compared to the spin-echo sequence with a 180° refocusing angle described in method (1).

Fig. 1
figure 1

Examples of ROIs (in red) drawn in pancreas for a STEAM spectroscopy and b T2-weighted imaging series acquired at different echo times

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Data processing

Mono-exponential decay with a non-linear least squares method was used to fit T2 relaxation times [21]; for the T2-weighted images magnitude signals were used and for the STEAM data the area under the curve of the water peak was used. To fit the T2 relaxation time from the lower refocusing angle series, the equivalent echo times (TEequiv) were used. This TEequiv was the calculated apparent echo time (based on the average T1 and T2 relaxation times determined with the 180° refocusing pulse and STEAM) as if a 180° refocusing angle had been used [22]. An ROI was manually drawn within the area with the best B1+ homogeneity and B1+ closest to 100%, excluding big vessels (Fig. 1b). The position of the ROI in the pancreas was consistent within subjects, however, between subjects the location of the ROI varied between head, body and tail of the pancreas. The signal in the ROIs was subsequently averaged and fitted. Average T1 and T2 relaxation times were calculated. Finally, age dependency was examined using all three datasets.

Statistical analysis

An unpaired t test was performed to compare T2 relaxation fitting methods (1) and (2). Since previously published research has shown a significant linear dependence of age with T1 relaxation times [23] and it is known that the pancreas tissue composition is changing with age [16], a linear regression analysis for age with respect to T1 and T2 was performed in SPSS (IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.).

Results

Out of 26 subjects, 22 T1 and 23 T2 datasets could be used for further analysis. The discarded datasets had insufficient image quality, caused by motion or not enough B1+ amplitude in the pancreas region. Average age of the subjects was 37 years (range 21–72 years) for the T1 datasets and 40 years (range 24–72 years) for the T2 datasets.

T1 relaxation times (mean ± std) for all 22 subjects are summarized in Fig. 2, the average T1 relaxation time was 896 ± 149 ms. An example of an B1+ map is shown in Fig. 3, the mean ratio of the measured B1+ over the expected B1+ value in the ROI across the subjects was 0.92 ± 0.14. Linear regression analysis showed no correlation between age and T1 relaxation time (slope = 1.1, offset = 856, R2 = 0.01, p = 0.6).

Fig. 2
figure 2

T1 relaxation times in a ROI in the pancreas for all individual subjects. The average T1 relaxation time was 896 ms with a standard deviation of 149 ms. The solid line indicates the average T1 relaxation time and the dashed lines indicate the mean ± the standard deviation

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Fig. 3
figure 3

Example of a B1+ map acquired after B1 shimming of the pancreas for a single subject. The image scaling represents the measured B1+ in percent from the aimed B1+ of 10 µT. ROI in black showing the region used for data analysis, an average B1+ of 100% is achieved

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Using method (1) (T2-weighted image series with a 180° refocusing pulse) and (2) (using STEAM spectroscopy) for T2 determinations gave an average T2 relaxation time of 28.1 ms (n = 3) and 25.6 (n = 4), respectively. An unpaired t test proved no significant difference (p = 0.6) between the results of the two methods. Combining these results as a reference value gave an average T2 of 26.7 ± 5.3 ms.

Method (3) resulted in a lower average T2 relaxation time of 19.5 ± 3.8 ms (n = 16) as expected due to the lower refocusing angle used. Fitted T2 relaxation times for all 23 subjects are summarized in Fig. 4. No correlation between age and T2 relaxation time was found (slope = − 0.1, offset = 31, R2 = 0.2, p = 0.07). Figure 5 shows examples of the mono-exponential fits for all three methods, with the signal of the first acquisition normalized to 1, for three single subjects.

Fig. 4
figure 4

T2 relaxation times in a ROI in the pancreas for all individual subjects. The average T2 relaxation time was 26.7 ms with a standard deviation of 5.3 ms. Triangles show the individual subjects measured with method (1) (T2-weighted image series with a refocusing pulse of 180°), circles show method (2) (STEAM spectroscopy) and the squares show method (3) (T2-weighted image series with a refocusing pulse of 35°). The solid line indicates the average T2 relaxation time from methods (1) and (2) and the dashed lines indicate the mean ± the standard deviation

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Fig. 5
figure 5

Individual T2 mono-exponential fits for all three methods for a single subject. Correspondence of the slope of the mono-exponential fits is shown. T2 relaxation times determined for these individual subjects using method (1)—T2-weighted image echo-series with 180° (triangles), method (2)—STEAM spectroscopy (circles) and method (3) 35° refocusing pulses (squares) were 34.3 ms, 28.3 ms and 23.1 ms, respectively

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Multi 2D T2-weighted single-shot turbo spin-echo images FA 90°, refocusing flip angle 35°, TE 80 ms (TEequiv = 31 ms), TR 10 s, TSE factor of 121, SPAIR fat suppression, voxel size of 1.5 × 1.5 × 5 mm3 (Fig. 6) were obtained. TEequiv close to the average T2 relaxation time of pancreas and TR more than 5 times longer ( ~ 11 times longer) than the average T1 relaxation time for improved contrast. The full field of view of the pancreas can be covered. However, signal voids can be still observed outside the region of interest (not B1+ optimized region), which are more pronounced in spin-echo-based sequences.

Fig. 6
figure 6

T2-weighted image for one subject using an equivalent echo time of 31 ms. 1.5 × 1.5 × 5 mm3 voxels. The red arrow points at the pancreas. Field inhomogeneities with signal voids outside the pancreas (blue arrow) can be observed. The yellow arrows point at regions where overtipping occurs (~ 180°) due to B1+ field inhomogeneity effects, leading to signal voids

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Discussion

In this study, we determined normal pancreas T1 and T2 relaxation times in 26 healthy subjects aged 21–72 years at 7 T. T1 and T2 relaxation times for pancreas at 7 T—to our knowledge—have not been reported before. However, they have been reported for pancreas in healthy subjects at 1.5 T and 3 T. In the literature, it can be found that T1 relaxation times increase and T2 relaxation times decrease with increasing field strengths [13, 23]. De Bazelaire et al. [13] used an inversion recovery method and different inversion times for T1 measurements and a multiple spin-echo (SE) technique with different echo times for T2 measurements in six healthy subjects, reported T1 values of 584 ± 14 ms for 1.5 T and 725 ± 71 ms for 3 T and T2 values of 46 ± 6 ms for 1.5 T and 43 ± 7 ms for 3 T, and concluded that pancreas T1 relaxation times increased and T2 relaxation times decreased with increasing field strength. Tirkes et al. [23] reported a mean T1 relaxation time of 797 ms at 3 T for healthy pancreas (n = 53, sequence: dual flip angle 3D gradient echo). A slightly higher mean T1 of 987 ± 52 ms and mean T2 of 50 ± 3 ms at 3 T was reported by Chhor et al. [15] (n = 6, sequence: Look-Locker for T1 and T2-prep for T2 measurements). Our 7 T results confirm the expected trend of increasing T1 and decreasing T2 relaxation times with age.

In addition, T1 and T2 values are dependent on tissue composition [24]. In this study, we did not investigate tissue differences between subjects. Therefore, we could not confirm this at 7 T. Tirkes et al. [23] also found a weak correlation between age and T1 relaxation time in the pancreas at 3 T, which we could not observe in our measurements at 7 T. The relatively young mean age of them could explain the lack of correlation (if any).

The use of standard TSE sequences attenuates the effect of molecular diffusion by the use of multiple refocusing pulses, the effect becoming stronger as the refocusing pulses get closer to each other [14, 24]. In addition, differences in imaging methods and determining T2 relaxation times, a more than doubled magnetic field strength, different age ranges, and the morphology of each subject, combined with the complex characteristics of tissues, may be responsible for the large decrease of T2 relaxation time found at 7 T.

For T1 measurements, a Look-Locker sequence is generally used with a TR (including the 6 s per cycle) of more than 5 times the T1 value of pancreas tissue, which is required to measure the T1 value accurately. Using T2-weighted imaging with full 180° refocusing angle and magnitude signals to fit the water peaks from the MR spectroscopy measurements, T2 relaxation times for pancreas could be correctly determined. A spin-echo sequence such as the one used here in method (1) is not practical to use in such large groups of subjects. The high SAR deposition in the body due to the large refocusing angles requires long repetition times leading to long scanning times, to keep SAR under the guideline levels. Since the mentioned SAR levels was the worst-case possible SAR and it is known that the dipole array will never exceed a local SAR of 10 W/kg when driven at a time averaged power of 3 W per channel driving all eight antennas at any phase setting, the SAR could be overestimated but were always within (conservative) limits. In addition, there are hardware limitations associated to these high-power demanding sequences. T2 imaging with a small refocusing pulse ensures a more practical sequence; with shorter scan times and lower SAR levels. However, T2 imaging with a 35° refocusing pulse is affected by T1-weighted stimulated echoes during the signal formation [25], which leads to a lengthening of the signal-intensity decay. This resulted in longer T2 relaxation times, which after correction with the equivalent echo times (to a 180° refocusing angle), resulted in slightly lower T2 relaxation values and a comparable variability to the results found with the nominal 180° refocusing pulse and the spectroscopy data, as was seen in Fig. 4. No other explanation could be found for the underestimation of the results of method (3). Age-dependency testing using data from method (3) is, therefore, only suitable for assessing the relative differences of T2 of the pancreas with respect to age.

Inter-subject variability in the measured relaxation times can be caused by different factors. Variations within characteristics of (pancreatic) tissue, and their change with age were different for individuals, even between men and women (which we did not take into account). As Sato et al. [16] describes in their paper, the pancreas changes with increasing age; characteristic changes with age are pancreatic atrophy, lobulation and fatty degeneration. These changes, such as the fraction of fat in the pancreas would lead to altered relaxation times.

Results were fitted over scans with different echo times since a single sequence with multiple echo times given by the turbo factor resulted to be too sensitive to motion and breathing artifacts that would result in blurring of the image. This leads to slight differences in anatomy position between echo times. Therefore, the delineated ROIs did not correspond to exactly the same anatomical position, leading to outliers and a higher variation in the raw data, which can influence the fitting. In our study, data were obtained from all regions in the pancreas. Since the ROIs were drawn in the area with the best B1+ homogeneity, the location was different between subjects. Tirkes et al. [23] showed a slight but not significant difference between the relaxation times measured in head, body or tail. As we have not accounted for these differences, this might have been another factor affecting the standard deviation in our calculations.

Lastly, imaging the abdomen at higher field, especially with T2-weighted sequences, is challenging. The scans are more sensitive to artifacts given the increased B0 and B1+ inhomogeneities (even with good B0 and B1+ shimming) found at higher field strengths, leading to greater standard deviations sources.

The measured T1 and T2 relaxation times for pancreas at 7 T reported here is a starting point for pancreatic research at higher field strengths to improve abdominal MR imaging, and may be a base for further use of MR techniques to noninvasive pancreatic diagnostics particularly in early stages of disease.

Conclusion

T1 and T2 relaxation times of the healthy pancreas were reported for 7 T, which can be used for image acquisition optimization. No significant correlation was found between age and T1 or T2 relaxation times of the pancreas.