Reduced field-of-view versus large field-of-view diffusion-weighted MRI in the evaluation of pancreatic lesions.

Introduction

Diffusion-weighted MR imaging (DWI) is a MR imaging technique based on the physical property of diffusion, which describes microscopic random movement of water molecules driven by their internal thermal energy. This movement is known as Brownian Motion and it is influenced by parameters like cell density, cell membrane integrity and cell viability. Therefore, DWI is a useful tool to assess the micro-structural organization of a tissue. Indeed, it allows to distinguish between a high-cellularity tissue, in which the movement of water molecules is restricted, and a low-cellularity tissue, in which this movement is permitted. This technique implies the application of diffusion-sensitizing gradients that cause decrease of MR signal when water molecules are free to move, while the signal intensity remains high when their motion is restricted.

DWI is applied to many organs, in both oncologic and non-oncologic populations; in particular it is an evolving tool to evaluate various pathologic conditions of the pancreas both qualitatively and quantitatively.

However, the limits of pancreas DWI include poor spatial resolution, the deep central location of the pancreas in the abdomen, the presence of several artifacts such as breathing artifacts, ghosting and susceptibility artifacts due to adjacent structures.

Recently a new DWI sequence, named as Field-of-View Optimized and Constrained Undistorted Single-Shot (FOCUS), has been developed to provide higher spatial resolution, and it has already been applied in the prostate (1-3), in the rectum (4), in the breast (5, 6) and preliminarily also in the pancreas (7-11). FOCUS consists in a reduced-FOV single shot diffusion weighted echo planar imaging sequence (SS DW EPI) in which a 2D spatially-selective echo-planar radio-frequency excitation pulse is used to reduce the excitation volume in both phase encoding and slice select directions.

This technique allows to reduce the FOV along the phase encoding direction and to reduce the number of k-space lines along that same direction, in order to obtain a higher spatial resolution within the same time of acquisition, reducing inhomogeneity artifacts.

The purpose of our study was to perform qualitative comparison of image quality and quantitative comparison of ADC values between reduced FOV and full FOV DWI sequences in patients with solid pancreatic lesions.

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Materials and methods

PATIENTS

Our radiological database was retrospectively searched between 2016 and 2020 to identify patients who were referred to our department for MR examinations of the upper abdomen for pancreato-biliary evaluation. The study population only included patients with solid pancreatic lesions larger than 1 cm that underwent both large FOV and reduced FOV DWI, and who did not undergo any prior oncologic treatment such as chemotherapy or radiation therapy (Figure 1). Based on these criteria, MR images were obtained from 60 patients (40 men and 20 women aged between 16 and 85 years; mean age, 59.93 ± 15.73 years). Of these, 30 patients underwent surgery (15 duodeno-cephalo-pancreatectomies, 14 distal pancreatectomies and 1 central pancreatectomy), 15 patients underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), while the remaining 15 patients underwent imaging and clinical follow-up. Our study population included 23 patients with ductal adenocarcinoma, 11 patients with neuroendocrine tumor, 9 patients with adenocarcinoma arising from intraductal papillary mucinous neoplasm, 7 patients with autoimmune pancreatitis, 5 patients with chronic pancreatitis, 3 patients with solid pseudopapillary tumor and 2 patients with pancreatic acinar cell carcinoma.

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MR IMAGING PROTOCOL

All MRI examinations were performed with a 3T device (GE Discovery MR750; GE Healthcare) using an eight-channel phased-array body coil. Patients had to fast at least 6 hours and, before starting the examination, scopolamine methyl-bromide was administered intramuscularly to avoid peristaltic artifacts.

Our MR imaging protocol of the pancreas included T2-w images, MRCP and T1-w images acquired before and after intravenous injection of Gadolinium-based contrast agents. (Figure 2). Before contrast administration, DWI was performed with two-dimensional (2D) fat suppressed respiratory triggered, spin-echo echo-planar DWI sequences (SE-EPI DWI), acquired in the axial plane with multiple b values (0, 500, 1000 s/mm2_{) in all diffusion}

directions, by using both conventional large FOV sequence and reduced FOV sequence (FOCUS) with a 2D spatially selective radiofrequency (RF) excitation pulse to reduce the FOV in the phase-encoding direction. Detailed imaging parameters of the standard MRI protocol and of both DWI sequences are listed in Tables 1 and 2, respectively.

Table 1: standard protocol for MRI examinations of the pancreas. The table shows the imaging parameters of each sequence. TR, repetition time; TE, echo time; FA, flip angle; BH, breath holding; RTr, Respiratory Trigger; * Effect Bandwith

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Table 2: Imaging parameters of reduced FoV and large FoV DWI. FoV, field of view; TR, repetition time; TE, echo time; FA, flip angle; BH, breath holding; RTr, Respiratory Trigger; * Effect Bandwith

2a 2b

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Fig. 2 Standard MRI protocol - 2a: Ax 3D Dual Echo T1w; 2b: Ax SSFSE T2w fatsat; 2c: Ax FS Propeller T2w; 2d: MRCP T2w; 2e: Ax DWI b=1000 s/mm2_{; 2f: Ax DWI FOCUS b=1000 s/mm}2_{; 2g: WATER Ax Turbo LAVA Flex; 2h:}

WATER Ax Turbo LAVA + mdc.

IMAGE ANALYSIS

Qualitative Analysis

Two radiologists (with 20 and 3 years of experience in abdominal MRI, respectively), both blinded to the pathological reports, independently performed qualitative analysis of all MR images on a dedicated workstation (Advantage Windows VolumeShare 4.7; GE Healthcare, Milwaukee, Wisconsin, USA). Reduced FOV and large FOV DWI (b=500 and b=1000 s/mm2₎

were randomly analyzed by the two readers using a 4-point scale (1 to 4) to evaluate 4 parameters, according to the criteria put forward by Kim et al. (7):

1) Sharpness (1, poorly visualized anatomy and non-diagnostic; 2, fairly delineated pancreas with margin blurring; 3, good delineation of pancreas with a sharp margin; 4, excellent sharpness of the pancreas or clear visualization of the pancreatic duct)

2) Distortion, ghosting, motion, and susceptibility artefacts (1, severe and non -diagnostic; 2, moderate; 3, mild; 4, absent)

2e 2f

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3) Lesion conspicuity (1, lesion not detectable; 2, merely recognizable lesion-to-background contrast; 3, intermediate lesion-to-background contrast or high contrast with indistinct lesion margin; 4, excellent lesion-to-background contrast and a clear lesion margin) 4) Overall image quality as a sum of the three parameters mentioned above.

Quantitative Analysis

The same two readers performed quantitative measurements of the ADC values of pancreatic lesions in consensus. T2-weighted images and enhanced T1-weighted images were available for better detection of lesions, if required. ADC values were measured using a mono-exponential fit, by drawing an ellipsoid region of interest (ROI) on b value = 1000 s/mm2_{images and automated}

ADC maps generated by the built-in software (GeniQ; GE Healthcare, Milwaukee, Wisconsin, USA), as already done and optimized in previous studies (12, 13). For each lesion, the ROI was placed on the same location on both sequences, taking care to avoid areas with artifacts, vessels, bile ducts and pancreatic ducts (Figure 7). In case of a multifocal disease, ROIs were placed on each focal lesion and the average ADC value was calculated.

STATISTICAL ANALYSIS

All statistical analyses were performed using SPSS v.26 (IBM SPSS Statistics, Armonk, NY, USA). Mean (SD) was used to describe qualitative scores and quantitative data. T-test for paired data was used to compare the qualitative image analysis scores and ADC values between reduced FOV and large FOV DWI sequences. Comparisons of image quality parameters were made using the average scores between the 2 readers. Inter-reader agreement for qualitative evaluation was assessed using t-test. A p value <0.05 was considered as statistical significance. Furthermore, Pearson and Spearman correlation coefficients were performed.

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Results

Qualitative Analysis

Reduced FOV DWI showed significantly better scores in sharpness (2.68 ± 0.71), artifacts (2.62 ± 0.71) and overall image quality (2.82 ± 0.73) as compared to large FOV DWI (sharpness: 2.45 ± 0.55; artifacts: 2.42 ± 0.58; overall image quality: 2.59 ± 0.56) (all p < 0.05). No significant difference in lesion conspicuity was noted between reduced FOV (2.89 ± 0.85) and large FOV DWI (2.78 ± 0.90) (p= 0.311) (Figures 3-6 and Table 3). For sharpness, both readers assigned a score of 4 (excellent sharpness of the pancreas or clear visualization of the pancreatic duct) to 5 cases in reduced FOV but only in 2 cases of large FOV DWI. Furthermore, this parameter received a score of 2 (fairly delineated pancreas with margin blurring) from both readers in 18 cases of reduced FOV and 25 cases of large FOV DWI. For artifacts, both readers assigned a score ≥ 3 (mild or absent) to 33 cases of reduced FOV and 24 cases of large FOV DWI. For lesion conspicuity, both readers assigned scores of 4 (excellent lesion-to-background contrast and clear lesion margin) to 14 cases in reduced FOV DWI and 11 cases in large FOV DWI. Finally, for overall image quality both readers assigned a score of 4 to 6 cases of reduced FOV and just 1 case of large FOV DWI.

The two readers were in agreement for all the qualitative parameters of large FOV sequences and for lesion conspicuity of reduced FOV sequences, while there was a significant difference for sharpness, artifacts and overall image quality of reduced FOV sequences (p < 0.05) (Table 4).

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Fig. 3. Large FOV (3a) and reduced FOV DWI (3b) with corresponding ADC maps in a patient with a neuroendocrine tumor. Note that the lobulated appearance of the pancreas and the pancreatic duct are more clearly visualized on reduced FOV DWI.

Fig. 4. Reduced FOV (4a) and large FOV DWI (4b) with corresponding ADC maps in a patient with ductal adenocarcinoma. Note how reduced FOV DWI is less affected by motion and susceptibility artifacts as compared to the conventional sequence.

ADC=1.13x10-9 m2/sec

b=500 sec/mm2 _{b=1000 sec/mm}2

b=500 sec/mm2 _{b=1000 sec/mm}2 ADC=1.16x10-9 m2/sec 3a

3b

4a

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Fig. 5. Large FOV (5a) and reduced FOV DWI (5b) with corresponding ADC maps in a patient with a neuroendocrine tumor. In both sequences the mass is well detectable and has a high lesion-to-background contrast, without significant differences in lesion conspicuity.

Fig. 6. Bar plot showing the distribution of the image quality scores in reduced FOV and large FOV DWI sequences with the corresponding p values. Sharpness, artifacts, and overall image quality demonstrated significantly higher scores in reduced FOV DWI.

ADC=0.95x10-9 m2/sec ADC=0.93x10-9 m2/sec 5a 5b b=500 sec/mm2 _{b=1000 sec/mm}2 b=500 sec/mm2 _{b=1000 sec/mm}2

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Table 3. Comparison of image quality parameters between reduced FOV and large FOV DWI sequences. Data are mean (standard deviation). T-test was performed to compare the two sequences using averaged scores of the two readers. FOV = field-of-view, DWI = diffusion-weighted imaging.

Parameter Large FOV

Reader 1 Reader 2

p value Reduced FOV

Reader 1 Reader 2

p value

Sharpness 2.43 (0.59) 2.52 (0.62) 0.228 2.53 (0.72) 2.82 (0.81) 0.001

Artifacts 2.45 (0.56) 2.38 (0.67) 0.252 2.5 (0.72) 2.73 (0.78) 0.001

Lesion Conspicuity 2.77 (0.93) 2.78 (0.96) 0.821 2.85 (0.92) 2.93 (0.88) 0.279

Overall Image Quality 2.58 (0.62) 2.60 (0.59) 0.766 2.7 (0.74) 2.95 (0.79) <0.001

Table 4. T-test was performed to assess inter-reader agreement for large FOV and reduced FOV DWI sequences. Reader 1 is the radiologist with 3 years of experience while reader 2 is the radiologist with 20 years of experience. Data are mean (standard deviation). The readers were in agreement for all the image quality parameters of large FOV DWI and for lesion conspicuity of reduced FOV DWI.

Quantitative Analysis

There was no significant difference between large FOV and reduced FOV DWI in the fitted ADC values of various solid pancreatic lesions (p > 0.05) (Figure 7).

The most frequent histologic subtype was ductal adenocarcinoma (23 cases), with mean ADC values of 1.32 x10-9_m2_{/s ± 0.21 and 1.33 x10}-9_m2_{/s ± 0.17 at reduced FOV and large FOV DWI,}

respectively. We found that autoimmune pancreatitis (7 cases) was the subtype with the lowest mean ADC values (1.22 x10-9_m2_{/s ± 0.21 and 1.17 x10}-9_m2_{/s ± 0.17 at reduced FOV and large}

FOV DWI, respectively). The mean ADC values of each histological subtype are listed in Table 5.

Sequence Sharpness Artifacts Lesion

Conspicuity

Overall Image Quality

Reduced FOV DWI 2.68 (0.71) 2.62 (0.71) 2.89 (0.85) 2.82 (0.73)

Large FOV DWI 2.45 (0.55) 2.42 (0.58) 2.78 (0.9) 2.59 (0.56)

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Fig. 7. Large FOV (7a) and reduced FOV DWI (7b) with corresponding ADC measurements in a patient with acinar cell carcinoma. No significant differences were noted between the two sequences.

Table 5. ADC measurements of different solid pancreatic lesions in reduced FOV and large FOV DWI. Data are mean (standard deviation). Histologic types with less than 5 patients are not shown. IPMC = intraductal papillary mucinous carcinoma.

Histologic type Chronic

Pancreatitis Autoimmune Pancreatitis Neuroendocrine Tumor Ductal Adenocarcinoma IPMC No. of Patients 5 7 11 23 9 ADC lFOV (x10-9_m2_/s) _{1.38 (0.23)} _{1.17 (0.17)} _{1.30 (0.28)} _{1.33 (0.17)} _{1.32 (0.18)} ADC rFOV (x10-9_m2_/s) _{1.41 (0.16)} _{1.22 (0.21)} _{1.31 (0.33)} _{1.32 (0.21)} _{1.33 (0.20)} 7a 7b ADC=0.91x10-9 m2/sec ADC=0.90x10-9 m2/sec b=1000 sec/mm2 b=1000 sec/mm2

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Discussion

In our study we evaluated image quality and ADC values of reduced FOV and large FOV DWI in a group of patients with solid pancreatic lesions. Our results indicated that reduced FOV DWI shows better sharpness and overall image quality, as well as significantly reduced image artifacts. On the other hand, the two sequences did not show significant differences in terms of lesion conspicuity. Besides, quantitative analysis highlighted that ADC values in solid pancreatic lesions on reduced FOV DWI are like those calculated on large FOV DWI, without any statistically significant difference.

Our study results agree with previous studies that compared reduced FOV and large FOV DWI of the pancreas (7, 8). In their study, Kim at al. found that reduced FOV DWI shows better anatomic structure visualization, lesion conspicuity and less artifacts than full FOV DWI, without significant differences in ADC values of pancreatic lesions between the two sequences. Although in their study the patient population was bigger (102 patients), they included both cystic and solid lesions, while we put effort in selecting only patients with solid lesions. In our opinion, another limitation of their study was that reduced FOV and full FOV DWI were acquired with different b values (0, 400 s/mm2_{and 0, 500 s/mm}2_{, respectively), and}

this might have affected qualitative image analysis and ADC measurements. In our study, instead, the b values were higher (0, 500 and 1000 s/mm2_{) and were the same in both}

sequences, allowing a more reliable comparison.

The first image quality parameter that we evaluated was sharpness, which represents the anatomic detail provided by the sequence. We noted that all the cases with the highest scores were adenocarcinomas, that generally cause a dilation of the main pancreatic duct, and therefore a clearer visualization of the duct itself. We suppose that the higher scores in sharpness of reduced FOV DWI might be related to the higher spatial resolution of this sequence, due to the reduced number of k-space lines required in the phase-encoding direction, which contributed to the better anatomic structure visualization.

The second analyzed parameter was the presence of artifacts, such as motion, susceptibility, and distortion artifacts. Reduced FOV DWI proved to be significantly less affected by these types of artifacts when compared to large FOV DWI. We suppose that the reduction of distortion artifacts is related to fewer acquisition steps of reduced FOV DWI. Furthermore, this sequence allows to reduce susceptibility artifacts by excluding air-tissue interfaces from the

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shim volume, and motion artifacts by excluding adjacent abdominal organs and aorta during scanning.

Lesion conspicuity was the only image quality parameter in which the two sequences did not show any significant difference, although the mean score of reduced FOV DWI was higher (2.89 ± 0.85) than that of large FOV DWI (2.78 ± 0.90). This means that both sequences have a similar reliability in detecting pancreatic lesions, but we noted that reduced FOV DWI provides a better visualization of the different components of the lesion, allowing to differentiate solid and cystic areas in more detail (Figure 8). This was particularly evident for adenocarcinomas arising from IPMN, in which the neoplastic degeneration could be better distinguished from the cystic part in reduced FOV DWI. We noticed that in some cases the hyperintensity of a lesion on DWI (and therefore a high score in lesion conspicuity) did not correspond to a low ADC value, which means that the lesion did not show a high diffusion restriction. This might be related to a T2 shine-through artifact, that leads to a hyperintensity on DWI (even at high b values) because of the intrinsic long T2 decay time of some tissues that “shines through” to the DWI image, rather than because of a real restricted diffusion. This artifact was present especially in some lesions with high perfusion, such as neuroendocrine tumors (Figure 9). Therefore, we should always confirm true restricted diffusion by measuring the ADC value, which is not influenced by the T2 shine-through artifact. We also noted that there was no difference in the scores of lesion conspicuity between benign and malignant lesions included in the study, and this could be due to the T2 shine-through artifact as well, causing even some benign lesions to be bright on DWI.

The last qualitative parameter evaluated is overall image quality, which represents a sum of all the previous parameters, and the scores were significantly better for reduced FOV DWI. For quantitative analysis, we calculated the mean ADC values of the pancreatic lesions divided by histological subtype in both sequences, including the only subtypes with at least 5 cases. No statistically significant difference was noted between reduced FOV and large FOV DWI (p > 0.05). We consider this result particularly important for the validation of reduced FOV DWI, since it shows that this sequence is reliable as much as the conventional one in assessing the diffusion restriction of pancreatic lesions.

We assessed that the readers were in agreement for all the image quality parameters of large FOV DWI and for lesion conspicuity of reduced FOV DWI, while there was not a strong

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agreement for sharpness, artifacts and overall image quality of reduced FOV DWI. We speculate that this difference might be due to the relatively recent introduction of reduced FOV DWI, therefore both readers did not have much experience in interpreting MR images obtained through this sequence. Despite these differences, when Pearson and Spearman coefficients were applied, they both showed a positive correlation between the scores. One limitation of our study is that it is a retrospective study, anyways it reflects our standard routine and clinical practice. Another limitation of the study is that the quantitative measurement of ADC values was performed in consensus and not independently by the two readers. We chose to use this method because of the different experience of the readers in placing the ROIs that could have affected the results, especially for smaller lesions. A training session for the reader with less experience prior to the investigation would be required in future studies in order to perform independent ADC measurements.

In conclusion, reduced FOV DWI provides better anatomic structure visualization, greater overall image quality and reduced imaging artifacts as compared to the conventional large FOV DWI. Therefore, reduced FOV DWI can be helpful for radiologists to evaluate oncologic and non-oncologic pancreatic diseases in better detail, and it could be included in the standard MRI protocol of the pancreas.

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Fig. 8. MR examination of a patient with adenocarcinoma arising from IPMN - 8a: T2wi, T1wi + Gd and MRCP showing a multiloculated cystic lesion in the body of the pancreas, with a solid component on its right side; 8b and 8c: large FOV and reduced FOV DWI, respectively, showing the cystic and solid components of the lesion, with the corresponding ADC maps. In this case, reduced FOV DWI allowed a better detection of the neoplastic degeneration. 8a 8b 8c b=0 sec/mm2 _{b=1000 sec/mm}2 b=1000 sec/mm2 b=0 sec/mm2

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Fig. 9. Reduced FOV (9a) and large FOV DWI (9b) and corresponding ADC measurements in a patient with a neuroendocrine tumor of the pancreas. The nodule has high lesion conspicuity (score 4) but shows a high ADC value after placing a ROI on the ADC map. This might be due to the elevated perfusion of the nodule, causing a T2 shine-through artifact. 9a a 9b ADC=1.55x10-9 m2/sec ADC=1.63x10-9 m2/sec b=1000 sec/mm2 b=1000 sec/mm2

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References

1. Shuai Maa, Kangjie Xua, Huihui Xiea, Huihui Wanga, Rui Wanga, Xiaodong Zhanga, Juan Weib, Xiaoying Wanga. Diagnostic efficacy of b value (2000 s/mm2) diffusion-weighted imaging for prostate cancer: Comparison of a reduced field of view sequence and a conventional technique. (European Journal of Radiology 107 (2018) 125–133)

2. Reishauer C at al. High-resolution diffusion tensor imaging of prostate cancer using a reduced FOV technique. (Eur J Radiology 2011; 80:e34-e41)

3. Brent A. Warndahla, Eric A. Borischa , Akira Kawashimab , Stephen J. Riederera , Adam T. Froemminga. Conventional vs. reduced field of view diffusion weighted imaging of the prostate: Comparison of image quality, correlation with histology, and interreader agreement. (Magnetic Resonance Imaging 47 2018; 67–76)

4. Peng Y, Li Z, Tang H, Wang Y, Hu X, Shen Y, Hu D. Comparison of reduced field-of-view diffusion-weighted imaging (DWI) and conventional DWI techniques in the assessment of rectal carcinoma at 3.0T: Image quality and histological T staging. (J Magn Reson Imaging. 2018 Apr;47(4):967-975. doi: 10.1002/jmri.25814. Epub 2017 Jul 10)

5. M.W. Barentsz, MD, PhD1, V. Taviani, PhD2, J.M. Chang, MD, PhD3, D.M. Ikeda, MD, PhD2, K.K. Miyake, MD, PhD4, S. Banerjee, PhD5, M.A.A.J van den Bosch, MD, PhD1, B.A. Hargreaves, PhD2, and B.L. Daniel, MD, PhD2. Assessment of tumor morphology on diffusion-weighted breast MRI: Diagnostic value of reduced-FOV High resolution DWI. (J Magn Reson Imaging. 2015 December; 42(6): 1656–1665. doi:10.1002/jmri.24929)

6. Park et al. Comparison of readout segmented echo-planar imaging (EPI) and EPI with reduced field-of-view diffusion-weighted imaging at 3T in patients with breast cancer. (J Magn Reson Imaging, 2015)

7. Hyungjin Kim, MD, Jeong Min Lee, MD, Jeong Hee Yoon, MD, Jin-Young Jang, MD , Sun-Whe Kim, MD , Ji Kon Ryu, MD , Stephan Kannengiesser, PhD , Joon Koo Han, MD, Byung Ihn Choi, MD. Reduced Field-of-View Diffusion-Weighted Magnetic Resonance Imaging of the Pancreas: Comparison with Conventional Single-Shot Echo-Planar Imaging. (Korean J Radiol 2015;16(6):1216-1225)

8. Mannelli L, Monti S, Corrias G, Fung MM, Nyman C, Golia Pernicka JS, Do RKG. Comparison of Navigator Triggering Reduced Field of View and Large Field of View Diffusion-Weighted Imaging of the Pancreas. (J Comput Assist Tomogr. 2019 Jan/Feb;43(1):143-148. doi: 10.1097/RCT.0000000000000778)

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9. Ma, Li, Pan et al. High resolution diffusion weighted magnetic resonance imaging of the pancreas using reduced field of view single-shot echo-planar imaging at 3 T. (Magn Reson Imaging, 2014; 32(2):125-31)

10. Thierfelder KM et al. Paraller-transmit-accelerated spatially-selective excitation MRI for reduced-FOV diffusion-weighted imaging of the pancreas. (Eur J Radiol, 2014; 83(10):1709-14)

11. Riffel et al. Zoomed EPI-DWI of the pancreas using two-dimensional spatially-selective radiofrequency excitation pulses. (PLoS One 2014; 9:e89488)

12. Donati et al. 3T diffusion-weighted MRI in the response assessment of colorectal liver metastases after chemotherapy: Correlation between ADC value and histological tumour regression grading (Eur J Radiol. 2017; 91:57-65)

13. Donati et al. 3 T MR perfusion of solid pancreatic lesions using dynamic contrast-enhanced DISCO sequence: Usefulness of qualitative and quantitative analyses in a pilot study. (Magn Reson Imaging. 2019; 59:105-113)