Prostate T2-Weighted Spin-Echo MRI With and Without Glucagon: A Paired Scan Quality Assessment

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Borisch, Adam T. Froemming, Akira Kawashima, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7217403/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Oct, 2025 Read the published version in Abdominal Radiology → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose To evaluate the effectiveness of subcutaneous glucagon in reducing motion artifact during prostate MRI through intraindividual comparison. Methods At our institution patients undergoing a clinical prostate MRI exam receive 1 mg of subcutaneous glucagon before scanning. From February 15, 2024 to February 11, 2025 33 such patients were recruited to undergo an additional, research exam without glucagon. All exams were acquired at 3T. An axial T2-weighted spin-echo series (T2-WI) was acquired within both exams. Evaluation of the T2-WI series was done by three experienced radiologists using the criteria of diagnostic quality (0–3 scale), PI-QUALv2 (0–3 sum), motion artifact (significant, visible, none), and reviewer preference (five-point relative scale). Due to differences in prescribed coverage, the scan times for the two T2-WI sequences were in general different for each subject. Results were stratified using the acquisition time ratio (T rel ) between the glucagon vs. non-glucagon scans. Wilcoxon tests assessed score differences. Results Across all 33 subjects, no significant differences were found between glucagon and non-glucagon scans. However, the observed negative correlation between glucagon preference and T rel (p = 0.026) led to stratification into low-T rel (n = 16) and high-T rel (n = 17) groups. In the low-T rel group the glucagon scans provided significantly improved diagnostic quality (p = 0.048), PI-QUALv2 sum (p = 0.049), motion scores (p = 0.047), and reader preference (p = 0.042). Conclusion Subcutaneous glucagon provides improved image quality in prostate T2-WI MRI when scan duration remains within 1.25× of that of a non-glucagon T2-WI series. The benefit appears to decrease with longer scan times. prostate MRI prostate cancer glucagon T2-weighted spin-echo Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 INTRODUCTION Magnetic resonance imaging has been shown to be fundamental in the diagnostic pathway of prostate MRI [ 1 ], and a critical sequence of both multi-parametric [ 2 ] and bi-parametric MRI [ 3 ] is the T2-weighted spin-echo (T2-WI) sequence. However, achieving optimal T2-WI image quality requires minimizing artifacts, particularly those caused by bowel peristalsis, which can degrade diagnostic accuracy [ 4 ]. To mitigate this, spasmolytic agents such as hyoscine N-butyl bromide (HBB), an anticholinergic agent also known as scopolamine butylbromide (Buscopan ®), and glucagon have been studied for their ability to suppress smooth muscle peristalsis prior to imaging [ 5 ]. The Prostate Imaging-Reporting and Data System (PI-RADS) was first introduced in 2012 to standardize the acquisition and interpretation of MRI in men suspected of having prostate cancer [ 6 ]. With advancements in MRI technology, subsequent updates in versions 2 [ 7 ] and 2.1 [ 2 ] provided more detailed technical considerations; however, they did not establish a definitive recommendation regarding the use of pharmacologic agents for motion artifact reduction, stating that there was no consensus on this issue. PI-RADS v2 acknowledged that anti-spasmodic agents, such as glucagon and scopolamine butylbromide, could be beneficial in some patients but were not universally necessary given the additional cost and potential adverse effects. The current PI-RADS v2.1 provided no updates. In the United States, glucagon, a polypeptide hormone produced by the alpha cells in the pancreatic islet of Langerhans, is FDA-approved as a diagnostic aid for gastrointestinal imaging due to its ability to induce bowel hypotonia, thereby improving visualization during imaging studies [ 8 ]. Glucagon can be administered via intravenous (IV), intramuscular (IM), or subcutaneous (SC) routes for diagnostic aid purposes, each with a distinct pharmacokinetic profile. IV glucagon acts rapidly, within approximately 1 minute, but is associated with a higher likelihood of side effects, including nausea, transient hypertension from its inotropic effects, and rare but severe hypersensitivity reactions such as hypotension, rash, or vomiting [ 8 , 9 ]. IM glucagon reaches peak plasma levels in approximately 13 minutes and has a mean half-life of 26 minutes, though its effectiveness can vary significantly between individuals [ 9 , 10 ]. SC glucagon reaches peak levels in 10–13 minutes and has a longer half-life of around 40 minutes, suggesting a more prolonged and stable reduction in bowel mobility [ 8 , 9 ]. Several studies have evaluated the impact of anti-spasmodic agents on prostate MRI, with HBB being the agent most frequently studied. Some research supports the routine use of HBB, showing significant improvements in image quality, particularly on T2-weighted (T2-WI) sequences [ 11 – 13 ]. These studies suggest that HBB preserves anatomical delineation by minimizing blurring from peristalsis-related motion artifacts [ 11 – 13 ]. However, other studies have challenged the routine use of HBB, with findings indicating that its effect on image quality is minimal and not mandatory for prostate MRI, particularly at higher field strengths such as 3.0 Tesla [ 14 – 16 ]. Glucagon has also been shown to have both benefits and limitations. A prospective intra-individual study [ 17 ] assessed the effect of 1 mg IV glucagon on small bowel motility using dynamic MRI over a one-hour period. The results showed that glucagon consistently induced complete and prolonged bowel paralysis (average duration of effect: 18 ± 7 minutes). However, another recent study [ 18 ] reported that IM-administered glucagon did not lead to a statistically significant improvement in overall prostate image quality. No studies have specifically evaluated SC glucagon for prostate MRI, despite its longer half-life, fewer side effects, and lower interindividual variability compared to IM and IV routes [ 8 , 19 ], and its effectiveness in routine clinical imaging remains unproven. The purpose of this study was to assess the effectiveness of SC glucagon in reducing motion artifacts during axial T2-WI prostate MRI by comparing series acquired with and without glucagon administration in the same subjects, providing a direct intra-individual evaluation METHODS AND MATERIALS Overall Approach and Study Design This retrospective study was conducted under an Institutional Review Board (IRB)-approved protocol in which all recruited subjects gave written informed consent. In our institutional clinical MRI practice glucagon is routinely administered subcutaneously prior to prostate MRI examinations to reduce bowel peristalsis unless contraindicated. The original pool of possible subjects for this study was comprised of male patients with suspected or confirmed prostate cancer who underwent clinically indicated prostate MRI between February 15, 2024, and February 11, 2025 (Group 1 in Fig. 1 ). These MRI exams with glucagon administration are referred to as “clinical” exams. From this group subjects were routinely recruited at a rate of about one per week to undergo a second, “research” exam, performed at our MRI research center (Group 2). These exams were generally done to assess the effect on image quality of some technical parameter such as in-plane resolution or an alternative receiver coil array. All research subjects still had an intact prostate gland, i.e. no subjects were post-prostatectomy. All research exams were performed without administration of glucagon. Also, research exams were performed without use of contrast material. For all subjects the clinical and research exams were performed within one day of each other. Because the clinical exam typically uses contrast material, if it was performed first, then at least 12 hours, typically overnight, was allowed for clearance of contrast material prior to performing the research exam. Patient preparation was identical for both exams: patients were asked to fast for at least three hours prior to the exam and void and evacuate the rectum immediately prior to the exam. For the clinical exam 1 mg glucagon (Nova Plus, Fresenius Kabi, Lake Zurich, IL, USA) was administered SC once the patient entered the scan room. Other than this, the initial sequences of the clinical and research exams were identical for each subject. Specifically, after placement of the patient on the table a 30-second localizer scan was performed of the pelvis. Next, sagittal T2-WI images were acquired in 2 minutes of the midline pelvis to localize the prostate, allowing patient-specific angulation for the slice select direction of the axial T2-WI images to align with the primary longitudinal axis of the prostate. The third sequence for each exam was generally the axial T2-WI series, and these clinical and research axial T2-WI series comprised the subject data sets for this work. Each exam then proceeded with additional series. MRI Acquisition The clinical and research exams were performed on 3.0 Tesla MRI scanners (GE Healthcare, Waukesha WI USA) with in-table posterior and blanket anterior coil arrays, each comprised of multiple five-element rows. 25 or 30 active elements total were active for each exam. No endorectal coils were used in any of the clinical or research exams. For each subject the same axial T2-WI sequence was used in the clinical and research exams. However, partway through the accumulation of subject data, in December 2024 the clinical axial T2-WI sequence was modified to allow equivalent in-plane resolution but 23% reduced acquisition time [ 20 ]. This modified sequence was then also used as the axial T2-WI sequence in the companion research exam. Parameters for these two T2-WI sequences are shown in Table 1 . Table 1 Acquisition parameters of the two T2-weighted spin-echo sequences Sequence Parameters Initial Sequence (N = 25) (before Dec 4, 2024) Updated Sequence (N = 8) (after Dec 4, 2024) Echo Time (TE) 150 ms 150 ms Repetition Time (TR) 3200–4600 ms 3200–4600 ms Matrix Size 400 × 230 320 × 280 In-plane resolution (area) 0.280 mm 2 0.285 mm 2 Signal Bandwidth ± 64 kHz ± 32 kHz Section Thickness and Spacing 3 mm, abutting 3 mm, abutting Echo Train Length 24 21 Number of Averages 2 1 Acquired No. Slices Clinical Exams (Median, min – max) 36, 30–40 34, 30–42 Acquired No. Slices Research Exams (Median, min – max) 30, 30–36 34, 32–34 Acquisition Time Clinical Exams (Median, min – max, min:sec) 3:55, 3:07 − 4:20 2:48, 2:18 − 3:29 Acquisition Time Research Exams (Median, min – max, min:sec) 3:04, 2:58 − 3:40 2:39, 2:34 − 2:43 After accumulation of the matched sets of axial T2-WI series from the 39 subjects, it was discovered that three of the exams used different reconstructions in the clinical vs. research series, causing significant SNR differences. Two exams had markedly extended (> 6 min) acquisition times due to Specific Absorption Rate considerations from implanted devices, and one exam had significant SNR loss in the clinical series due to a technical coil issue. These six exams were excluded from analysis, resulting in the final data set comprised of 33 matched studies (Group 3 of Fig. 1 ). For each subject the clinical and research exams were performed by different MR technologists. Thus, although the same axial T2-WI sequence was used for both exams, there was some variability in the obliquity of the axial slices as well as in the number of axial slices for the desired superior-inferior coverage. Because the repetition time in two-dimensional multi-slice acquisition is adjusted to accommodate the desired number of slices, this led to differences in the acquisition times of the clinical vs. research exams. Evaluation A total of 66 axial T2WI series were evaluated, two each (clinical series with glucagon and research series without glucagon) from each of 33 subjects. Image series were evaluated by three radiologist readers (AF, AK, NT), all with over 10 years’ experience in prostate MRI. Each reviewer evaluated all series. To provide consistency, all series were trimmed to include only the central 30 slices, thereby equalizing the number of slices evaluated across both series for each subject. Evaluation was performed in two passes. In the first pass, each of the 66 T2-WI series was evaluated individually with the series presented in random order. In the second pass both clinical and research axial T2-WI series for each subject were presented simultaneously with the order randomized. For both passes all sequence- and patient-related information was removed. The signal ranges for each series were normalized to permit the same window and level for viewing, facilitating comparing the two series in the second pass. Images were viewed using Visage 7 client software (Visage Imaging, San Diego, CA, USA). In the first pass of evaluation each series was evaluated using three sets of evaluation criteria. The first was a four-point (0-to-3) scale for diagnostic quality (DQ) developed and used by our reviewers previously [ 20 , 21 ] prior to the definition of PI-QUALv2 [ 22 ]. The scale is defined as follows: DQ 0 = obviously non-diagnostic, severely limited by markedly poor SNR, gross motion or other artifact, or otherwise non-interpretable DQ 1 = marginally non-diagnostic, with SNR, resolution, or artifact limiting interpretation, generally requiring a rescan DQ 2 = non-ideal in quality such as due to slight blurring but still allowing interpretation DQ 3 = high diagnostic quality Evaluations were based on SNR, sharpness, and level of any artifact interfering with assessment of the prostate. For inter-reader calibration, prior to the evaluation all readers were presented with four exams at each DQ score, not part of the study, scored in consensus [ 21 ]. Each series was also evaluated for image quality using the PI-QUALv2 criteria [ 22 ] for axial T2WI. For all exams, both clinical and research series met the essential requirement for 3 mm thick axial slices. The three other criteria (SNR, delineation, and artifact) for the axial series were each evaluated as adequate or not using a Y/N (1/0) scale. For each series type, clinical (with glucagon) and research (no glucagon), results for the sum of criteria (integer scores 0–3) were tabulated. For calibration, prior to review all readers were provided images from the original work [ 22 ] which showed sample Y/N scores. The third evaluation criterion for the first pass was simply one of severity of motion artifact: 0: Significant; artifact severe enough to degrade the ability to interpret the image series 1: Visible; motion artifact present but with minimal diagnostic impact 2: None: no artifact present The second pass was a comparison in which the two series for each subject (randomly presented as A and B) were evaluated for preference using a five-point scale: -2 = strongly prefer series A -1 = prefer series A 0 = prefer neither series + 1: prefer series B + 2: strongly prefer Series B Statistical Analysis For each evaluation, scores from all three reviewers were averaged to generate a final composite score. The differences in DQ score, PI-QUALv2 sum score, motion severity score, and reader preference from the null result were evaluated using the Wilcoxon signed-rank test [ 23 ], with statistical significance set at p < 0.05. To assess inter-reader consistency Cohen’s κ [ 24 ] was calculated with interpretation according to Landis et.al study [ 25 ]. Preliminary analysis indicated that the clinical T2-WI series consistently required longer acquisition time than the research series, due to prescription of a larger number of slices in the former. To assess the potential impact of scan duration on image quality, a relative time ratio (T rel ) was defined for each subject as the ratio of the scan time for the series acquired with glucagon to that without glucagon. A plot of reader preference score vs. T rel suggested a negative correlation, and regression estimates were made using a constant and linear fits [ 26 ]. Based on the T rel median value (1.25), subjects were categorized into Low T rel (< 1.25) and High T rel (≥ 1.25) groups for subgroup analysis. RESULTS Demographics and Imaging Timing Clinical and research T2-WI series from a total of 33 cases were evaluated. Patient demographics are summarized in Table 2 . Table 2 Patient Demographics Age Range 52–79 years, median 68 Weight Range 60.3-119.3 kg, median 93 BMI Range 20.1–35.7 kg/m 2 , median 29.3 PSA Range 0.1–13.2 ng/ml, median: 6.3 Prostate Volume Range 12–110 cc, median: 50 Treatment Treatment-naïve, n = 27 PI-RADS 2, n = 9 PI-RADS 3, n = 4 PI-RADS 4, n = 10 PI-RADS 5, n = 4 Post-treatment for prostate cancer, n = 6 MRI guided cryo-ablation, n = 3 Chemotherapy + Androgen deprivation therapy, n = 2 Chemotherapy, n = 1 The ranges and median acquisition times for the clinical and research T2-WI series are shown in Table 1 . The values indicate a generally longer scan time for the clinical series, reflecting a higher number of prescribed slices in clinical exams. Evaluation of Reader Preference Figure 2 A is a histogram of the average reader preference scores for all 33 studies. There is no statistical preference for either the clinical (with glucagon) or research (without glucagon) series. However, when each score is plotted vs. its corresponding T rel value (Fig. 2 B), there appears to be preference for glucagon for low T rel as well as a clear trend for diminished preference as T rel increases. The line of regression is shown, and the linear fit is statistically superior (p < 0.026) vs. fitting the data to a constant. This observation led us to separate analysis of those 16 studies with T rel < 1.25, identified as blue dots, and of those 17 remaining studies with T rel ≥1.25 (red dots). Figure 2 C shows reader preference for the 16 studies with T rel 1.25 and indicates no preference with or without use of glucagon. Based on this finding, analysis of the evaluations from the first pass (DQ, PI-QUALv2, motion severity) was also performed for all studies as well as separately for the group with T rel < 1.25 and the group with T rel ≥1.25. Evaluations of Individual Series Analogous to Fig. 2 A, histograms of DQ, PI-QUALv2 sum, and level of motion artifact for all 33 studies showed no significant preference for the clinical (glucagon) or research (no glucagon) series. Also, analysis of the subgroup with T rel >1.25 showed no preference. These histograms are provided in Supplemental Fig. 1. Results of the evaluation of the subgroup with T rel < 1.25 are shown in Figs. 3 A-C for DQ, PI-QUALv2 sum, and motion severity, respectively. Mean values (µ) are shown for each. For all three evaluation criteria the superiority of the clinical (glucagon) series is statistically significant. Inter-reader agreement matrices showing the Cohen’s κ scores are shown in Fig. 4 . Values ranged from 0.47 to 0.65 for Diagnostic Quality (Fig. 4 A), 0.47 to 0.51 for PI-QUALv2 sum (Fig. 4 B), both showing moderate agreement, 0.71 to 0.72 for Prostate Motion (Fig. 4 C) showing substantial agreement, and 0.75 to 0.83 for Preference (Fig. 4 D), showing substantial to almost perfect agreement. Figures 5 – 7 show representative image results. DISCUSSION In this retrospective study of 33 subjects, we evaluated the impact of subcutaneous glucagon administration on image quality of prostate T2-WI MRI using an intraindividual comparison designed to minimize inter-patient variability and potential bias. To ensure consistency, both scans for each subject used the same T2-weighted pulse sequence, the T2-WI series was nominally run as the same series (generally third) within both exams, and all paired clinical and research scans were performed within a one-day interval. In this study, we found that subcutaneous glucagon administration improved image quality when scan durations with and without glucagon were closely matched. In the Low T rel group, defined as cases where scan time with glucagon was within 1.25× of the non-glucagon scan time, glucagon was associated with significantly higher diagnostic quality (DQ), PI-QUALv2 sum scores, reduced motion artifacts, and greater reader preference. For the High T rel group we speculate that the motion reduction of the glucagon was likely negated by the increased likelihood of motion artifact associated with the prolonged scan time. These findings are consistent with the general notion that reduction of the probability of motion increases the likelihood of improved diagnostic quality in prostate T2-WI MRI. Here, the likelihood of motion was reduced via administration of glucagon. An alternative is to reduce the motion likelihood via reduced acquisition time. Improved image quality has been demonstrated for fixed resolution and coverage by using acceleration based on deep learning reconstruction [ 27 , 28 ] or scan time reduction by reapportionment of the individual in-plane resolution parameters [ 20 ]. In assessing image quality of a T2-WI series perhaps a relevant threshold is that separating interpretable from non-diagnostic scans. For the latter a rescan may well be required, extending exam time and disrupting workflow. Such a threshold is subject to definition, but this might be taken as a DQ score < 1.5 (four cases for the No Glucagon (NG) cases in Fig. 3 A), a PI-QUALv2 sum < 1.5 (three NG cases in Fig. 3 B), or prostate motion less than midway between significant and visible (three NG cases in Fig. 3 C). For each of these metrics, the use of glucagon either eliminated (Fig. 3 C) or significantly reduced (Figs. 3 A, B) this number of likely rescans. The possible beneficial effect of glucagon in pelvic MRI has been studied previously. In female pelvic imaging, Sheikh-Sarraf et al. [ 29 ] demonstrated that IV glucagon administration significantly reduced motion artifacts and improved visualization of pelvic organs. Froehlich et al. [ 5 ] further showed in a dynamic prostate MRI study that IV glucagon induced a complete arrest of bowel motion in all volunteers and provided a prolonged period of bowel paralysis. However, data specifically addressing the role of glucagon in routine clinical prostate MRI remain limited. In the largest available study, Sundaram et al. [ 18 ] retrospectively evaluated the effect of IM glucagon on prostate MRI image quality and no significant difference in overall image quality was observed. However, unlike our intraindividual comparison approach, their study compared separate patient groups, which introduces greater potential for unaccounted variability. Our study assessed glucagon effectiveness after administration by SC injection, which offers pharmacokinetic advantages over other routes, including reduced intraindividual variability, avoidance of rapid plasma fluctuations, and a sustained antiperistaltic effect over the typical imaging window [ 8 , 10 ]. Due to differences in the obliquity and number of slices, the scan times for the clinical and research T2-WI series were not identical, with the clinical series generally longer. This was generally based on technologist preference rather than clinical necessity. This variation resulted in time discordance between paired scans which may have contributed to the reduced effect observed in discordant pairs. This study has several limitations. As explained, variability in scan duration limited our ability to standardize acquisition time across all pairs which restricts our ability to isolate the impact of scan duration on glucagon efficacy. Additionally, while glucagon was consistently administered immediately after patient positioning, the interval between injection and the T2-weighted sequence acquisition varied, depending on sequence order or unforeseen workflow delays, potentially introducing variability in drug effect at the time of imaging. Finally, the modest sample size and retrospective design may limit the generalizability of our findings. Future prospective studies with standardized scan protocols and tighter control over sequence duration may be needed to confirm and expand upon these results. CONCLUSION Subcutaneous glucagon administration improves image quality in prostate MRI, reflected in higher DQ and PI-QUAL scores, reduced motion artifacts, and greater reviewer preference. These benefits were seen when the duration of the glucagon scan remained within 1.25× that of non-glucagon scans but diminished with longer acquisitions. Our findings support its selective use when shorter scan times can be achieved, maximizing its contribution to diagnostic image quality. Declarations Author Contribution All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by S.H. and E.B. The manuscript was prepared by S.H. and S.R., and all authors read and approved the final manuscript. Acknowledgement We would like to acknowledge Kathy J. Brown and Corey C. Woxland, R.T. for assistance with the human studies. References Schoots IG, Padhani AR (2020) Delivering clinical impacts of the MRI diagnostic pathway in prostate cancer diagnosis. Abdom Radiol (NY) 45:4012–4022. https://doi.org/10.1007/s00261-020-02547-x Turkbey B, Rosenkrantz AB, Haider MA, et al (2019) Prostate imaging reporting and data system version 2.1: 2019 update of prostate imaging reporting and data system version 2. 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John Wiley & Sons Gassenmaier S, Afat S, Nickel D, et al (2021) Deep learning-accelerated T2-weighted imaging of the prostate: reduction of acquisition time and improvement of image quality. Eur J Radiol 137:109600. https://doi.org/10.1016/j.ejrad.2021.109600 Oerther B, Engel H, Nedelcu A, et al (2024) Performance of an ultra-fast deep-learning accelerated MRI screening protocol for prostate cancer compared to a standard multiparametric protocol. Eur Radiol 34:7053–7062. https://doi.org/10.1007/s00330-024-10776-7 Sheikh-Sarraf M, Nougaret S, Forstner R, Kubik-Huch RA (2020) Patient preparation and image quality in female pelvic MRI: recommendations revisited. Eur Radiol 30:5374–5383. https://doi.org/10.1007/s00330-020-06869-8 Additional Declarations No competing interests reported. Supplementary Files SupplementalFigure1.png Supplemental Figure 1. Paired histograms of (A) diagnostic quality, (B) PI-QUAL sum, and (C) prostate motion scores for all 33 cases. Paired histograms of (D) diagnostic quality, (E) PI-QUAL sum, and (F) prostate motion scores for the 17 cases in which T rel ≥ 1.25. In all six plots there is no significant difference between the No Glucagon and Glucagon groups. Mean values (µ) for each histogram are also indicated. SupplementalVideo1.mp4 Supplemental Video 1. Side-by-side comparison of the T2-WI series of the non-glucagon scan (left) and glucagon scan (right) from Subject #25 (Figure 5). SupplementalVideo2.mp4 Supplemental Video 2. Side-by-side comparison of the T2-WI series of the non-glucagon scan (left) and glucagon scan (right) from Subject #32 (Figure 6). SupplementalVideo3.mp4 Supplemental Video 3. Side-by-side comparison of the T2-WI series of the non-glucagon scan (left) and glucagon scan (right) from Subject #28 (Figure 7). Cite Share Download PDF Status: Published Journal Publication published 13 Oct, 2025 Read the published version in Abdominal Radiology → Version 1 posted Editorial decision: Revision requested 11 Aug, 2025 Reviews received at journal 10 Aug, 2025 Reviews received at journal 29 Jul, 2025 Reviewers agreed at journal 29 Jul, 2025 Reviewers agreed at journal 28 Jul, 2025 Reviewers invited by journal 27 Jul, 2025 Editor assigned by journal 26 Jul, 2025 Submission checks completed at journal 26 Jul, 2025 First submitted to journal 25 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7217403","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":492915292,"identity":"9c551c5f-ea40-470f-b052-b2fbde29e162","order_by":0,"name":"Sara Hassanzadeh","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Hassanzadeh","suffix":""},{"id":492915293,"identity":"294691fe-cd2d-4407-b63d-d36ba25b8922","order_by":1,"name":"Eric A. Borisch","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Eric","middleName":"A.","lastName":"Borisch","suffix":""},{"id":492915294,"identity":"9bbbcebc-2d29-4fc3-8fe8-e7db708a8284","order_by":2,"name":"Adam T. Froemming","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Adam","middleName":"T.","lastName":"Froemming","suffix":""},{"id":492915295,"identity":"9965d62d-6c74-4f4e-a60a-3e61a8931473","order_by":3,"name":"Akira Kawashima","email":"","orcid":"","institution":"Mayo Clinic Arizona","correspondingAuthor":false,"prefix":"","firstName":"Akira","middleName":"","lastName":"Kawashima","suffix":""},{"id":492915296,"identity":"132dbf60-45c5-4299-b1ae-7612b687471a","order_by":4,"name":"Naoki Takahashi","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Naoki","middleName":"","lastName":"Takahashi","suffix":""},{"id":492915297,"identity":"b35acd42-15c9-4725-9b58-3d0de73a5dfc","order_by":5,"name":"Stephen J. Riederer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYDACZgYGCRDND+UzNhCtRbKBaC0MUC0GB4jVYt7OfPDGxz02+cbXDj+T+MBgI7vhAAEtMofZki1nPEuz3HY7zUxyBkOaMUEtEsw8ZtI8Bw4bmN1OADIYDicSoYX/m/SfA/8NjGenfwNq+U+MFh42aYYDBwwMpHNAthwgRgubsWXPgWQDids5xZYzDJKNZxLUwn/44Y0fB+wM+Genb7zxocJOto+QFmTAIsFgQIJyEGD+QKKGUTAKRsEoGCEAALQWPoN6UzrNAAAAAElFTkSuQmCC","orcid":"","institution":"Mayo Clinic","correspondingAuthor":true,"prefix":"","firstName":"Stephen","middleName":"J.","lastName":"Riederer","suffix":""}],"badges":[],"createdAt":"2025-07-25 22:08:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7217403/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7217403/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00261-025-05215-0","type":"published","date":"2025-10-13T15:58:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88092699,"identity":"e1c284c2-8a19-404c-ab82-2c4fc037513c","added_by":"auto","created_at":"2025-08-01 10:34:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":171437,"visible":true,"origin":"","legend":"\u003cp\u003eFlow of selection of subjects\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/c677c2265ee04264a18c9519.png"},{"id":88092700,"identity":"ec5c914d-56e7-43bb-8793-388a880d9169","added_by":"auto","created_at":"2025-08-01 10:34:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":188508,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Histogram showing the distribution of reader-averaged preferences across all participants (N = 33), indicating no overall preference (p = 0.723). (B) Plot of reader preference for glucagon vs. relative scan time. Each point represents the reader-averaged preference score for an individual participant (ordinate) plotted against the relative scan time (T\u003csub\u003erel\u003c/sub\u003e) (abscissa).\u0026nbsp; Points are color-coded by T\u003csub\u003erel \u003c/sub\u003egroup: blue for Low T\u003csub\u003erel\u003c/sub\u003e (\u0026lt; 1.25, N=16), red for High T\u003csub\u003erel \u003c/sub\u003e(≥ 1.25, N=17). The dashed regression line shows a statistically significant negative correlation between reader preference and T\u003csub\u003erel \u003c/sub\u003e(slope = –0.036, p = 0.026), indicating that reader preference for glucagon decreases consistently as relative scan time increases. (C) Histogram of average preferences in the Low T\u003csub\u003erel \u003c/sub\u003esubgroup (N = 16), showing a significant preference for the glucagon scans (p = 0.042).\u0026nbsp; (D) Histogram of average preferences in the High T\u003csub\u003erel\u003c/sub\u003e subgroup (N = 17), showing no significant preference (p = 0.180).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/7d33e919708864d03344afe8.png"},{"id":88092710,"identity":"639caed9-9975-4a35-8c1b-62fadfa0559b","added_by":"auto","created_at":"2025-08-01 10:34:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":219485,"visible":true,"origin":"","legend":"\u003cp\u003ePaired histograms of reader-averaged (A) diagnostic quality, (B) PI-QUAL sum, and (C) prostate motion scores in the Low T\u003csub\u003erel\u003c/sub\u003e group.\u0026nbsp; Lines connect the two scores for each participant for the no-glucagon scan (left) and glucagon scan (right).\u0026nbsp; Mean values (µ) for each histogram are also indicated.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/01441168d08d34121f3e6cea.png"},{"id":88092702,"identity":"00330762-8edb-4a6a-abea-39dee05dbb6f","added_by":"auto","created_at":"2025-08-01 10:34:39","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":232181,"visible":true,"origin":"","legend":"\u003cp\u003eCohen’s κ scores showing inter-reader agreement for (A) preference, (B) diagnostic quality, (C) PI-QUAL sum, and (D) prostate motion.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/7281101deb629d9aec614c89.png"},{"id":88093856,"identity":"f85c0228-5148-4c5b-8e30-20da7b47445d","added_by":"auto","created_at":"2025-08-01 10:42:39","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":346962,"visible":true,"origin":"","legend":"\u003cp\u003eImages of the full 16 cm field of view from (A) non-glucagon and (B) glucagon T2-WI scans from Subject #25, a 63-year-old man with biopsy-proven prostate cancer on active surveillance. \u0026nbsp;The non-glucagon and glucagon scan times were 3:11 and 3:37, respectively (T\u003csub\u003erel\u003c/sub\u003e = 1.1).\u0026nbsp; Reader-averaged DQ score improved from 1.33 (A) to 3 (B), and PI-QUAL sum from 1.33 to 3, effectively converting a likely non-diagnostic scan into a diagnostic-quality one.\u0026nbsp; Supplemental Video 1 compares the full image series and illustrates the marked slice-to-slice displacement for the non-glucagon series, causing reduced scores.\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/e76d4e80a6a2314b745507db.jpeg"},{"id":88093854,"identity":"5762453f-f012-4e64-b922-dc9f012d6f03","added_by":"auto","created_at":"2025-08-01 10:42:39","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":342947,"visible":true,"origin":"","legend":"\u003cp\u003eImages of the full 16 cm field of view from (A) non-glucagon and (B) glucagon T2-WI scans from Subject #32, a 69-year-old man with biopsy-confirmed prostate cancer on active surveillance, with one PI-RADS 4 and one PI-RADS 5 lesion. The non-glucagon and glucagon scan times were 2:41 and 2:52, respectively (T\u003csub\u003erel\u003c/sub\u003e = 1.05).\u0026nbsp; Reader-averaged DQ improved from 1.33 to 3.0, and PI-QUAL sum from 1.67 to 3, converting a marginally diagnostic scan into a diagnostic-quality one. Supplemental Video 2 compares the full image series.\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/be2b2e9300b478b46d03521e.jpeg"},{"id":88093861,"identity":"e43a071f-4184-407d-9f64-d05f38f6a1d8","added_by":"auto","created_at":"2025-08-01 10:42:39","extension":"jpeg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":334032,"visible":true,"origin":"","legend":"\u003cp\u003eImages of the full 16 cm field of view from (A) non-glucagon and (B) glucagon T2-WI scans from Subject #28, a 66-year-old man with biopsy-proven prostate cancer.\u0026nbsp; The glucagon and non-glucagon scan times were 2:37 and 2:43, respectively (T\u003csub\u003erel\u003c/sub\u003e = 0.96). Reader-averaged DQ score improved from 2 (A) to 2.67 (B), and PI-QUAL sum from 2.33 to 2.67, improving an already good-quality scan, primarily by reducing the subtle blur and slight slice-to-slice displacement, seen in the companion Supplemental Video 3 comparing the full series.\u003c/p\u003e","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/623ed322414aa52f955b4137.jpeg"},{"id":93956029,"identity":"91c48931-97be-4211-9555-7c5e1706aa5f","added_by":"auto","created_at":"2025-10-20 16:09:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2355564,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/ead36cf1-7841-4ef0-8d88-e3d08a0f50cf.pdf"},{"id":88092697,"identity":"ff849948-3a8a-4462-aad4-f9ba6cf8f5cf","added_by":"auto","created_at":"2025-08-01 10:34:39","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":843639,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Figure 1\u003c/strong\u003e. Paired histograms of (A) diagnostic quality, (B) PI-QUAL sum, and (C) prostate motion scores for all 33 cases.\u0026nbsp; Paired histograms of (D) diagnostic quality, (E) PI-QUAL sum, and (F) prostate motion scores for the 17 cases in which T\u003csub\u003erel\u003c/sub\u003e\u0026nbsp; ≥ 1.25.\u0026nbsp; In all six plots there is no significant difference between the No Glucagon and Glucagon groups.\u0026nbsp; Mean values (µ) for each histogram are also indicated.\u003c/p\u003e","description":"","filename":"SupplementalFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/c13a760cbc08f6ea32abe490.png"},{"id":88092719,"identity":"92b61697-b67d-436c-8455-eb1c174c8b5d","added_by":"auto","created_at":"2025-08-01 10:34:39","extension":"mp4","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":17272912,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Video 1.\u003c/strong\u003e Side-by-side comparison of the T2-WI series of the non-glucagon scan (left) and glucagon scan (right) from Subject #25 (Figure 5).\u003c/p\u003e","description":"","filename":"SupplementalVideo1.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/588434b986001d338bcdb706.mp4"},{"id":88092720,"identity":"54335273-f134-4fed-ae73-a7c64e8f4a84","added_by":"auto","created_at":"2025-08-01 10:34:39","extension":"mp4","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":19037392,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Video 2\u003c/strong\u003e. Side-by-side comparison of the T2-WI series of the non-glucagon scan (left) and glucagon scan (right) from Subject #32 (Figure 6).\u003c/p\u003e","description":"","filename":"SupplementalVideo2.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/d8e1e019cd23047ceb4ddeb3.mp4"},{"id":88092721,"identity":"5976505b-a54b-4f82-9808-f5928d4d967a","added_by":"auto","created_at":"2025-08-01 10:34:39","extension":"mp4","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":16675921,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Video 3\u003c/strong\u003e. Side-by-side comparison of the T2-WI series of the non-glucagon scan (left) and glucagon scan (right) from Subject #28 (Figure 7).\u003c/p\u003e","description":"","filename":"SupplementalVideo3.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7217403/v1/1d01e75b90f47d66a4a2357b.mp4"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prostate T2-Weighted Spin-Echo MRI With and Without Glucagon: A Paired Scan Quality Assessment","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eMagnetic resonance imaging has been shown to be fundamental in the diagnostic pathway of prostate MRI [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and a critical sequence of both multi-parametric [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and bi-parametric MRI [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] is the T2-weighted spin-echo (T2-WI) sequence. However, achieving optimal T2-WI image quality requires minimizing artifacts, particularly those caused by bowel peristalsis, which can degrade diagnostic accuracy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. To mitigate this, spasmolytic agents such as hyoscine N-butyl bromide (HBB), an anticholinergic agent also known as scopolamine butylbromide (Buscopan ®), and glucagon have been studied for their ability to suppress smooth muscle peristalsis prior to imaging [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The Prostate Imaging-Reporting and Data System (PI-RADS) was first introduced in 2012 to standardize the acquisition and interpretation of MRI in men suspected of having prostate cancer [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. With advancements in MRI technology, subsequent updates in versions 2 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and 2.1 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] provided more detailed technical considerations; however, they did not establish a definitive recommendation regarding the use of pharmacologic agents for motion artifact reduction, stating that there was no consensus on this issue. PI-RADS v2 acknowledged that anti-spasmodic agents, such as glucagon and scopolamine butylbromide, could be beneficial in some patients but were not universally necessary given the additional cost and potential adverse effects. The current PI-RADS v2.1 provided no updates.\u003c/p\u003e\u003cp\u003eIn the United States, glucagon, a polypeptide hormone produced by the alpha cells in the pancreatic islet of Langerhans, is FDA-approved as a diagnostic aid for gastrointestinal imaging due to its ability to induce bowel hypotonia, thereby improving visualization during imaging studies [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Glucagon can be administered via intravenous (IV), intramuscular (IM), or subcutaneous (SC) routes for diagnostic aid purposes, each with a distinct pharmacokinetic profile. IV glucagon acts rapidly, within approximately 1 minute, but is associated with a higher likelihood of side effects, including nausea, transient hypertension from its inotropic effects, and rare but severe hypersensitivity reactions such as hypotension, rash, or vomiting [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. IM glucagon reaches peak plasma levels in approximately 13 minutes and has a mean half-life of 26 minutes, though its effectiveness can vary significantly between individuals [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. SC glucagon reaches peak levels in 10–13 minutes and has a longer half-life of around 40 minutes, suggesting a more prolonged and stable reduction in bowel mobility [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSeveral studies have evaluated the impact of anti-spasmodic agents on prostate MRI, with HBB being the agent most frequently studied. Some research supports the routine use of HBB, showing significant improvements in image quality, particularly on T2-weighted (T2-WI) sequences [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e–\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These studies suggest that HBB preserves anatomical delineation by minimizing blurring from peristalsis-related motion artifacts [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e–\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, other studies have challenged the routine use of HBB, with findings indicating that its effect on image quality is minimal and not mandatory for prostate MRI, particularly at higher field strengths such as 3.0 Tesla [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e–\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eGlucagon has also been shown to have both benefits and limitations. A prospective intra-individual study [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] assessed the effect of 1 mg IV glucagon on small bowel motility using dynamic MRI over a one-hour period. The results showed that glucagon consistently induced complete and prolonged bowel paralysis (average duration of effect: 18 ± 7 minutes). However, another recent study [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] reported that IM-administered glucagon did not lead to a statistically significant improvement in overall prostate image quality. No studies have specifically evaluated SC glucagon for prostate MRI, despite its longer half-life, fewer side effects, and lower interindividual variability compared to IM and IV routes [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and its effectiveness in routine clinical imaging remains unproven.\u003c/p\u003e\u003cp\u003eThe purpose of this study was to assess the effectiveness of SC glucagon in reducing motion artifacts during axial T2-WI prostate MRI by comparing series acquired with and without glucagon administration in the same subjects, providing a direct intra-individual evaluation\u003c/p\u003e"},{"header":"METHODS AND MATERIALS","content":"\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eOverall Approach and Study Design\u003c/span\u003e\u003c/p\u003e\u003cp\u003eThis retrospective study was conducted under an Institutional Review Board (IRB)-approved protocol in which all recruited subjects gave written informed consent.\u003c/p\u003e\u003cp\u003eIn our institutional clinical MRI practice glucagon is routinely administered subcutaneously prior to prostate MRI examinations to reduce bowel peristalsis unless contraindicated. The original pool of possible subjects for this study was comprised of male patients with suspected or confirmed prostate cancer who underwent clinically indicated prostate MRI between February 15, 2024, and February 11, 2025 (Group 1 in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). These MRI exams with glucagon administration are referred to as “clinical” exams. From this group subjects were routinely recruited at a rate of about one per week to undergo a second, “research” exam, performed at our MRI research center (Group 2). These exams were generally done to assess the effect on image quality of some technical parameter such as in-plane resolution or an alternative receiver coil array. All research subjects still had an intact prostate gland, i.e. no subjects were post-prostatectomy. All research exams were performed without administration of glucagon. Also, research exams were performed without use of contrast material.\u003c/p\u003e\u003cp\u003eFor all subjects the clinical and research exams were performed within one day of each other. Because the clinical exam typically uses contrast material, if it was performed first, then at least 12 hours, typically overnight, was allowed for clearance of contrast material prior to performing the research exam. Patient preparation was identical for both exams: patients were asked to fast for at least three hours prior to the exam and void and evacuate the rectum immediately prior to the exam.\u003c/p\u003e\u003cp\u003eFor the clinical exam 1 mg glucagon (Nova Plus, Fresenius Kabi, Lake Zurich, IL, USA) was administered SC once the patient entered the scan room. Other than this, the initial sequences of the clinical and research exams were identical for each subject. Specifically, after placement of the patient on the table a 30-second localizer scan was performed of the pelvis. Next, sagittal T2-WI images were acquired in 2 minutes of the midline pelvis to localize the prostate, allowing patient-specific angulation for the slice select direction of the axial T2-WI images to align with the primary longitudinal axis of the prostate. The third sequence for each exam was generally the axial T2-WI series, and these clinical and research axial T2-WI series comprised the subject data sets for this work. Each exam then proceeded with additional series.\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eMRI Acquisition\u003c/span\u003e\u003c/p\u003e\u003cp\u003eThe clinical and research exams were performed on 3.0 Tesla MRI scanners (GE Healthcare, Waukesha WI USA) with in-table posterior and blanket anterior coil arrays, each comprised of multiple five-element rows. 25 or 30 active elements total were active for each exam. No endorectal coils were used in any of the clinical or research exams.\u003c/p\u003e\u003cp\u003eFor each subject the same axial T2-WI sequence was used in the clinical and research exams. However, partway through the accumulation of subject data, in December 2024 the clinical axial T2-WI sequence was modified to allow equivalent in-plane resolution but 23% reduced acquisition time [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This modified sequence was then also used as the axial T2-WI sequence in the companion research exam. Parameters for these two T2-WI sequences are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAcquisition parameters of the two T2-weighted spin-echo sequences\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSequence Parameters\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInitial Sequence\u003c/p\u003e\u003cp\u003e(N = 25)\u003c/p\u003e\u003cp\u003e(before Dec 4, 2024)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eUpdated Sequence\u003c/p\u003e\u003cp\u003e(N = 8)\u003c/p\u003e\u003cp\u003e(after Dec 4, 2024)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEcho Time (TE)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e150 ms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e150 ms\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRepetition Time (TR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e3200–4600 ms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3200–4600 ms\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMatrix Size\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e400 × 230\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e320 × 280\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIn-plane resolution (area)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e0.280 mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.285 mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSignal Bandwidth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e± 64 kHz\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e± 32 kHz\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSection Thickness and Spacing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e3 mm, abutting\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 mm, abutting\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEcho Train Length\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of Averages\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcquired No. Slices Clinical Exams (Median, min – max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e36, 30–40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34, 30–42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcquired No. Slices Research Exams (Median, min – max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e30, 30–36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34, 32–34\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcquisition Time Clinical Exams (Median, min – max, min:sec)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e3:55, 3:07 − 4:20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2:48, 2:18 − 3:29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcquisition Time Research Exams (Median, min – max, min:sec)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e3:04, 2:58 − 3:40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2:39, 2:34 − 2:43\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003eAfter accumulation of the matched sets of axial T2-WI series from the 39 subjects, it was discovered that three of the exams used different reconstructions in the clinical vs. research series, causing significant SNR differences. Two exams had markedly extended (\u0026gt; 6 min) acquisition times due to Specific Absorption Rate considerations from implanted devices, and one exam had significant SNR loss in the clinical series due to a technical coil issue. These six exams were excluded from analysis, resulting in the final data set comprised of 33 matched studies (Group 3 of Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFor each subject the clinical and research exams were performed by different MR technologists. Thus, although the same axial T2-WI sequence was used for both exams, there was some variability in the obliquity of the axial slices as well as in the number of axial slices for the desired superior-inferior coverage. Because the repetition time in two-dimensional multi-slice acquisition is adjusted to accommodate the desired number of slices, this led to differences in the acquisition times of the clinical vs. research exams.\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eEvaluation\u003c/span\u003e\u003c/p\u003e\u003cp\u003eA total of 66 axial T2WI series were evaluated, two each (clinical series with glucagon and research series without glucagon) from each of 33 subjects. Image series were evaluated by three radiologist readers (AF, AK, NT), all with over 10 years’ experience in prostate MRI. Each reviewer evaluated all series. To provide consistency, all series were trimmed to include only the central 30 slices, thereby equalizing the number of slices evaluated across both series for each subject. Evaluation was performed in two passes. In the first pass, each of the 66 T2-WI series was evaluated individually with the series presented in random order. In the second pass both clinical and research axial T2-WI series for each subject were presented simultaneously with the order randomized. For both passes all sequence- and patient-related information was removed. The signal ranges for each series were normalized to permit the same window and level for viewing, facilitating comparing the two series in the second pass. Images were viewed using Visage 7 client software (Visage Imaging, San Diego, CA, USA).\u003c/p\u003e\u003cp\u003eIn the first pass of evaluation each series was evaluated using three sets of evaluation criteria. The first was a four-point (0-to-3) scale for diagnostic quality (DQ) developed and used by our reviewers previously [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] prior to the definition of PI-QUALv2 [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The scale is defined as follows:\u003c/p\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eDQ 0 = obviously non-diagnostic, severely limited by markedly poor SNR, gross motion or other artifact, or otherwise non-interpretable\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eDQ 1 = marginally non-diagnostic, with SNR, resolution, or artifact limiting interpretation, generally requiring a rescan\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eDQ 2 = non-ideal in quality such as due to slight blurring but still allowing interpretation\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eDQ 3 = high diagnostic quality\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eEvaluations were based on SNR, sharpness, and level of any artifact interfering with assessment of the prostate. For inter-reader calibration, prior to the evaluation all readers were presented with four exams at each DQ score, not part of the study, scored in consensus [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eEach series was also evaluated for image quality using the PI-QUALv2 criteria [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] for axial T2WI. For all exams, both clinical and research series met the essential requirement for 3 mm thick axial slices. The three other criteria (SNR, delineation, and artifact) for the axial series were each evaluated as adequate or not using a Y/N (1/0) scale. For each series type, clinical (with glucagon) and research (no glucagon), results for the sum of criteria (integer scores 0–3) were tabulated. For calibration, prior to review all readers were provided images from the original work [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] which showed sample Y/N scores.\u003c/p\u003e\u003cp\u003eThe third evaluation criterion for the first pass was simply one of severity of motion artifact:\u003c/p\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e0: Significant; artifact severe enough to degrade the ability to interpret the image series\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e1: Visible; motion artifact present but with minimal diagnostic impact\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e2: None: no artifact present\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003cp\u003eThe second pass was a comparison in which the two series for each subject (randomly presented as A and B) were evaluated for preference using a five-point scale:\u003c/p\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e-2 = strongly prefer series A\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e-1 = prefer series A\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e0 = prefer neither series\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e+ 1: prefer series B\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e+ 2: strongly prefer Series B\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003e For each evaluation, scores from all three reviewers were averaged to generate a final composite score. The differences in DQ score, PI-QUALv2 sum score, motion severity score, and reader preference from the null result were evaluated using the Wilcoxon signed-rank test [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], with statistical significance set at p \u0026lt; 0.05. To assess inter-reader consistency Cohen’s κ [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] was calculated with interpretation according to Landis et.al study [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePreliminary analysis indicated that the clinical T2-WI series consistently required longer acquisition time than the research series, due to prescription of a larger number of slices in the former. To assess the potential impact of scan duration on image quality, a relative time ratio (T\u003csub\u003erel\u003c/sub\u003e) was defined for each subject as the ratio of the scan time for the series acquired with glucagon to that without glucagon. A plot of reader preference score vs. T\u003csub\u003erel\u003c/sub\u003e suggested a negative correlation, and regression estimates were made using a constant and linear fits [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Based on the T\u003csub\u003erel\u003c/sub\u003e median value (1.25), subjects were categorized into Low T\u003csub\u003erel\u003c/sub\u003e (\u0026lt; 1.25) and High T\u003csub\u003erel\u003c/sub\u003e (≥ 1.25) groups for subgroup analysis.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eDemographics and Imaging Timing\u003c/span\u003e\u003c/p\u003e\u003cp\u003eClinical and research T2-WI series from a total of 33 cases were evaluated. Patient demographics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatient Demographics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAge Range\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52\u0026ndash;79 years, median 68\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eWeight Range\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60.3-119.3 kg, median 93\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eBMI Range\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20.1\u0026ndash;35.7 kg/m\u003csup\u003e2\u003c/sup\u003e, median 29.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003ePSA Range\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1\u0026ndash;13.2 ng/ml, median: 6.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eProstate Volume Range\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12\u0026ndash;110 cc, median: 50\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eTreatment-na\u0026iuml;ve, n\u0026thinsp;=\u0026thinsp;27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePI-RADS 2, n\u0026thinsp;=\u0026thinsp;9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePI-RADS 3, n\u0026thinsp;=\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePI-RADS 4, n\u0026thinsp;=\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePI-RADS 5, n\u0026thinsp;=\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003ePost-treatment for prostate cancer, n\u0026thinsp;=\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMRI guided cryo-ablation, n\u0026thinsp;=\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eChemotherapy\u0026thinsp;+\u0026thinsp;Androgen deprivation therapy, n\u0026thinsp;=\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eChemotherapy, n\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe ranges and median acquisition times for the clinical and research T2-WI series are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The values indicate a generally longer scan time for the clinical series, reflecting a higher number of prescribed slices in clinical exams.\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eEvaluation of Reader Preference\u003c/span\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA is a histogram of the average reader preference scores for all 33 studies. There is no statistical preference for either the clinical (with glucagon) or research (without glucagon) series. However, when each score is plotted vs. its corresponding T\u003csub\u003erel\u003c/sub\u003e value (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB), there appears to be preference for glucagon for low T\u003csub\u003erel\u003c/sub\u003e as well as a clear trend for diminished preference as T\u003csub\u003erel\u003c/sub\u003e increases. The line of regression is shown, and the linear fit is statistically superior (p\u0026thinsp;\u0026lt;\u0026thinsp;0.026) vs. fitting the data to a constant. This observation led us to separate analysis of those 16 studies with T\u003csub\u003erel\u003c/sub\u003e \u0026lt; 1.25, identified as blue dots, and of those 17 remaining studies with T\u003csub\u003erel\u003c/sub\u003e \u0026ge;1.25 (red dots). Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC shows reader preference for the 16 studies with T\u003csub\u003erel\u003c/sub\u003e \u0026lt; 1.25, indicating statistically significant preference (p\u0026thinsp;=\u0026thinsp;0.042) for the use of glucagon. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD shows reader preference for the 17 studies with T\u003csub\u003erel\u003c/sub\u003e \u0026gt;1.25 and indicates no preference with or without use of glucagon.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eBased on this finding, analysis of the evaluations from the first pass (DQ, PI-QUALv2, motion severity) was also performed for all studies as well as separately for the group with T\u003csub\u003erel\u003c/sub\u003e \u0026lt; 1.25 and the group with T\u003csub\u003erel\u003c/sub\u003e \u0026ge;1.25.\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eEvaluations of Individual Series\u003c/span\u003e\u003c/p\u003e\u003cp\u003eAnalogous to Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, histograms of DQ, PI-QUALv2 sum, and level of motion artifact for all 33 studies showed no significant preference for the clinical (glucagon) or research (no glucagon) series. Also, analysis of the subgroup with T\u003csub\u003erel\u003c/sub\u003e \u0026gt;1.25 showed no preference. These histograms are provided in Supplemental Fig.\u0026nbsp;1.\u003c/p\u003e\u003cp\u003eResults of the evaluation of the subgroup with T\u003csub\u003erel\u003c/sub\u003e \u0026lt; 1.25 are shown in Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA-C for DQ, PI-QUALv2 sum, and motion severity, respectively. Mean values (\u0026micro;) are shown for each. For all three evaluation criteria the superiority of the clinical (glucagon) series is statistically significant.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e Inter-reader agreement matrices showing the Cohen\u0026rsquo;s κ scores are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Values ranged from 0.47 to 0.65 for Diagnostic Quality (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA), 0.47 to 0.51 for PI-QUALv2 sum (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB), both showing moderate agreement, 0.71 to 0.72 for Prostate Motion (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC) showing substantial agreement, and 0.75 to 0.83 for Preference (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD), showing substantial to almost perfect agreement.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFigures \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e show representative image results.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this retrospective study of 33 subjects, we evaluated the impact of subcutaneous glucagon administration on image quality of prostate T2-WI MRI using an intraindividual comparison designed to minimize inter-patient variability and potential bias. To ensure consistency, both scans for each subject used the same T2-weighted pulse sequence, the T2-WI series was nominally run as the same series (generally third) within both exams, and all paired clinical and research scans were performed within a one-day interval.\u003c/p\u003e\u003cp\u003eIn this study, we found that subcutaneous glucagon administration improved image quality when scan durations with and without glucagon were closely matched. In the Low T\u003csub\u003erel\u003c/sub\u003e group, defined as cases where scan time with glucagon was within 1.25\u0026times; of the non-glucagon scan time, glucagon was associated with significantly higher diagnostic quality (DQ), PI-QUALv2 sum scores, reduced motion artifacts, and greater reader preference. For the High T\u003csub\u003erel\u003c/sub\u003e group we speculate that the motion reduction of the glucagon was likely negated by the increased likelihood of motion artifact associated with the prolonged scan time.\u003c/p\u003e\u003cp\u003eThese findings are consistent with the general notion that reduction of the probability of motion increases the likelihood of improved diagnostic quality in prostate T2-WI MRI. Here, the likelihood of motion was reduced via administration of glucagon. An alternative is to reduce the motion likelihood via reduced acquisition time. Improved image quality has been demonstrated for fixed resolution and coverage by using acceleration based on deep learning reconstruction [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] or scan time reduction by reapportionment of the individual in-plane resolution parameters [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn assessing image quality of a T2-WI series perhaps a relevant threshold is that separating interpretable from non-diagnostic scans. For the latter a rescan may well be required, extending exam time and disrupting workflow. Such a threshold is subject to definition, but this might be taken as a DQ score\u0026thinsp;\u0026lt;\u0026thinsp;1.5 (four cases for the No Glucagon (NG) cases in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA), a PI-QUALv2 sum\u0026thinsp;\u0026lt;\u0026thinsp;1.5 (three NG cases in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB), or prostate motion less than midway between significant and visible (three NG cases in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). For each of these metrics, the use of glucagon either eliminated (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC) or significantly reduced (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, B) this number of likely rescans.\u003c/p\u003e\u003cp\u003eThe possible beneficial effect of glucagon in pelvic MRI has been studied previously. In female pelvic imaging, Sheikh-Sarraf et al. [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] demonstrated that IV glucagon administration significantly reduced motion artifacts and improved visualization of pelvic organs. Froehlich et al. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] further showed in a dynamic prostate MRI study that IV glucagon induced a complete arrest of bowel motion in all volunteers and provided a prolonged period of bowel paralysis. However, data specifically addressing the role of glucagon in routine clinical prostate MRI remain limited. In the largest available study, Sundaram et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] retrospectively evaluated the effect of IM glucagon on prostate MRI image quality and no significant difference in overall image quality was observed. However, unlike our intraindividual comparison approach, their study compared separate patient groups, which introduces greater potential for unaccounted variability.\u003c/p\u003e\u003cp\u003eOur study assessed glucagon effectiveness after administration by SC injection, which offers pharmacokinetic advantages over other routes, including reduced intraindividual variability, avoidance of rapid plasma fluctuations, and a sustained antiperistaltic effect over the typical imaging window [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Due to differences in the obliquity and number of slices, the scan times for the clinical and research T2-WI series were not identical, with the clinical series generally longer. This was generally based on technologist preference rather than clinical necessity. This variation resulted in time discordance between paired scans which may have contributed to the reduced effect observed in discordant pairs.\u003c/p\u003e\u003cp\u003eThis study has several limitations. As explained, variability in scan duration limited our ability to standardize acquisition time across all pairs which restricts our ability to isolate the impact of scan duration on glucagon efficacy. Additionally, while glucagon was consistently administered immediately after patient positioning, the interval between injection and the T2-weighted sequence acquisition varied, depending on sequence order or unforeseen workflow delays, potentially introducing variability in drug effect at the time of imaging. Finally, the modest sample size and retrospective design may limit the generalizability of our findings. Future prospective studies with standardized scan protocols and tighter control over sequence duration may be needed to confirm and expand upon these results.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eSubcutaneous glucagon administration improves image quality in prostate MRI, reflected in higher DQ and PI-QUAL scores, reduced motion artifacts, and greater reviewer preference. These benefits were seen when the duration of the glucagon scan remained within 1.25\u0026times; that of non-glucagon scans but diminished with longer acquisitions. Our findings support its selective use when shorter scan times can be achieved, maximizing its contribution to diagnostic image quality.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by S.H. and E.B. The manuscript was prepared by S.H. and S.R., and all authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to acknowledge Kathy J. Brown and Corey C. Woxland, R.T. for assistance with the human studies.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSchoots IG, Padhani AR (2020) Delivering clinical impacts of the MRI diagnostic pathway in prostate cancer diagnosis. Abdom Radiol (NY) 45:4012\u0026ndash;4022. https://doi.org/10.1007/s00261-020-02547-x\u003c/li\u003e\n\u003cli\u003eTurkbey B, Rosenkrantz AB, Haider MA, et al (2019) Prostate imaging reporting and data system version 2.1: 2019 update of prostate imaging reporting and data system version 2. Eur Urol 76:340\u0026ndash;351. https://doi.org/10.1016/j.eururo.2019.02.033\u003c/li\u003e\n\u003cli\u003ePadhani AR, Schoots I, Villeirs G (2021) Contrast medium or no contrast medium for prostate cancer diagnosis. 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European Urology 69:16\u0026ndash;40. https://doi.org/10.1016/j.eururo.2015.08.052\u003c/li\u003e\n\u003cli\u003eMorris CH, Baker J (2025) Glucagon. In: StatPearls. StatPearls Publishing, Treasure Island (FL)\u003c/li\u003e\n\u003cli\u003eU.S. Food and Drug Administration (2022) Glucagon injection [prescribing information]\u003c/li\u003e\n\u003cli\u003eGutzeit A, Binkert CA, Koh D-M, et al (2012) Evaluation of the anti-peristaltic effect of glucagon and hyoscine on the small bowel: comparison of intravenous and intramuscular drug administration. Eur Radiol 22:1186\u0026ndash;1194. https://doi.org/10.1007/s00330-011-2366-1\u003c/li\u003e\n\u003cli\u003eUllrich T, Quentin M, Schmaltz AK, et al (2018) Hyoscine butylbromide significantly decreases motion artefacts and allows better delineation of anatomic structures in mp-MRI of the prostate. Eur Radiol 28:17\u0026ndash;23. https://doi.org/10.1007/s00330-017-4940-7\u003c/li\u003e\n\u003cli\u003eSlough RA, Caglic I, Hansen NL, et al (2018) Effect of hyoscine butylbromide on prostate multiparametric MRI anatomical and functional image quality. Clin Radiol 73:216.e9-216.e14. https://doi.org/10.1016/j.crad.2017.07.013\u003c/li\u003e\n\u003cli\u003eBoschheidgen M, Drewes L, Valentin B, et al (2025) Use of deep learning-accelerated T2 TSE for prostate MRI: comparison with and without hyoscine butylbromide admission. Magn Reson Imaging 118:110358. https://doi.org/10.1016/j.mri.2025.110358\u003c/li\u003e\n\u003cli\u003eRoethke MC, Kuru TH, Radbruch A, et al (2013) Prostate magnetic resonance imaging at 3 tesla: is administration of hyoscine-N-butyl-bromide mandatory? World J Radiol 5:259\u0026ndash;263. https://doi.org/10.4329/wjr.v5.i7.259\u003c/li\u003e\n\u003cli\u003eWagner M, Rief M, Busch J, et al (2010) Effect of butylscopolamine on image quality in MRI of the prostate. 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Eur Radiol Exp 9:44. https://doi.org/10.1186/s41747-025-00584-z\u003c/li\u003e\n\u003cli\u003ede Rooij M, Allen C, Twilt JJ, et al (2024) PI-QUAL version 2: an update of a standardised scoring system for the assessment of image quality of prostate MRI. Eur Radiol 34:7068\u0026ndash;7079. https://doi.org/10.1007/s00330-024-10795-4\u003c/li\u003e\n\u003cli\u003eRosner BA (2006) Fundamentals of biostatistics. Thomson-Brooks/Cole\u003c/li\u003e\n\u003cli\u003eCohen J (1968) Weighted kappa: nominal scale agreement with provision for scaled disagreement or partial credit. Psychol Bull 70:213\u0026ndash;220. https://doi.org/10.1037/h0026256\u003c/li\u003e\n\u003cli\u003eLandis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33:159. https://doi.org/10.2307/2529310\u003c/li\u003e\n\u003cli\u003eRencher AC, Schaalje GB (2008) Linear models in statistics. John Wiley \u0026amp; Sons\u003c/li\u003e\n\u003cli\u003eGassenmaier S, Afat S, Nickel D, et al (2021) Deep learning-accelerated T2-weighted imaging of the prostate: reduction of acquisition time and improvement of image quality. Eur J Radiol 137:109600. https://doi.org/10.1016/j.ejrad.2021.109600\u003c/li\u003e\n\u003cli\u003eOerther B, Engel H, Nedelcu A, et al (2024) Performance of an ultra-fast deep-learning accelerated MRI screening protocol for prostate cancer compared to a standard multiparametric protocol. Eur Radiol 34:7053\u0026ndash;7062. https://doi.org/10.1007/s00330-024-10776-7\u003c/li\u003e\n\u003cli\u003eSheikh-Sarraf M, Nougaret S, Forstner R, Kubik-Huch RA (2020) Patient preparation and image quality in female pelvic MRI: recommendations revisited. Eur Radiol 30:5374\u0026ndash;5383. https://doi.org/10.1007/s00330-020-06869-8\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"abdominal-radiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aima","sideBox":"Learn more about [Abdominal Radiology](http://link.springer.com/journal/261)","snPcode":"261","submissionUrl":"https://submission.springernature.com/new-submission/261/3","title":"Abdominal Radiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"prostate MRI, prostate cancer, glucagon, T2-weighted spin-echo","lastPublishedDoi":"10.21203/rs.3.rs-7217403/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7217403/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eTo evaluate the effectiveness of subcutaneous glucagon in reducing motion artifact during prostate MRI through intraindividual comparison.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eAt our institution patients undergoing a clinical prostate MRI exam receive 1 mg of subcutaneous glucagon before scanning. From February 15, 2024 to February 11, 2025 33 such patients were recruited to undergo an additional, research exam without glucagon. All exams were acquired at 3T. An axial T2-weighted spin-echo series (T2-WI) was acquired within both exams. Evaluation of the T2-WI series was done by three experienced radiologists using the criteria of diagnostic quality (0\u0026ndash;3 scale), PI-QUALv2 (0\u0026ndash;3 sum), motion artifact (significant, visible, none), and reviewer preference (five-point relative scale). Due to differences in prescribed coverage, the scan times for the two T2-WI sequences were in general different for each subject. Results were stratified using the acquisition time ratio (T\u003csub\u003erel\u003c/sub\u003e) between the glucagon vs. non-glucagon scans. Wilcoxon tests assessed score differences.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAcross all 33 subjects, no significant differences were found between glucagon and non-glucagon scans. However, the observed negative correlation between glucagon preference and T\u003csub\u003erel\u003c/sub\u003e (p\u0026thinsp;=\u0026thinsp;0.026) led to stratification into low-T\u003csub\u003erel\u003c/sub\u003e (n\u0026thinsp;=\u0026thinsp;16) and high-T\u003csub\u003erel\u003c/sub\u003e (n\u0026thinsp;=\u0026thinsp;17) groups. In the low-T\u003csub\u003erel\u003c/sub\u003e group the glucagon scans provided significantly improved diagnostic quality (p\u0026thinsp;=\u0026thinsp;0.048), PI-QUALv2 sum (p\u0026thinsp;=\u0026thinsp;0.049), motion scores (p\u0026thinsp;=\u0026thinsp;0.047), and reader preference (p\u0026thinsp;=\u0026thinsp;0.042).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eSubcutaneous glucagon provides improved image quality in prostate T2-WI MRI when scan duration remains within 1.25\u0026times; of that of a non-glucagon T2-WI series. The benefit appears to decrease with longer scan times.\u003c/p\u003e","manuscriptTitle":"Prostate T2-Weighted Spin-Echo MRI With and Without Glucagon: A Paired Scan Quality Assessment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-01 10:34:34","doi":"10.21203/rs.3.rs-7217403/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-11T10:35:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-11T03:28:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-29T23:00:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"335059989554721494336370488719950628601","date":"2025-07-29T18:06:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"181854876373920546397688764696447065125","date":"2025-07-28T04:35:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-27T13:42:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-26T12:20:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-26T12:18:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Abdominal Radiology","date":"2025-07-25T21:56:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"abdominal-radiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aima","sideBox":"Learn more about [Abdominal Radiology](http://link.springer.com/journal/261)","snPcode":"261","submissionUrl":"https://submission.springernature.com/new-submission/261/3","title":"Abdominal Radiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c7e3e7be-8ad9-4bb9-bbec-5bcee1d5ef94","owner":[],"postedDate":"August 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-20T16:02:55+00:00","versionOfRecord":{"articleIdentity":"rs-7217403","link":"https://doi.org/10.1007/s00261-025-05215-0","journal":{"identity":"abdominal-radiology","isVorOnly":false,"title":"Abdominal Radiology"},"publishedOn":"2025-10-13 15:58:00","publishedOnDateReadable":"October 13th, 2025"},"versionCreatedAt":"2025-08-01 10:34:34","video":"","vorDoi":"10.1007/s00261-025-05215-0","vorDoiUrl":"https://doi.org/10.1007/s00261-025-05215-0","workflowStages":[]},"version":"v1","identity":"rs-7217403","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7217403","identity":"rs-7217403","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}