Development of a standardized MRI protocol for pancreas assessment in humans

Virostko, John; Craddock, R. Cameron; Williams, Jonathan M.; Triolo, Taylor M.; Hilmes, Melissa A.; Kang, Hakmook; Du, Liping; Wright, Jordan; Kinney, Mara; Maki, Jeffrey H.; Medved, Milica; Waibel, Michaela; Kay, Thomas W. H.; Thomas, Helen E.; Greeley, Siri Atma W.; Steck, Andrea K.; Moore, Daniel J.; Powers, Alvin C.

doi:10.1371/journal.pone.0256029

Cited by 11 publications

(8 citation statements)

References 38 publications

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“…E : Postprandial UCPCRs of indicated participants; two family members (participants 4 and 5) were unavailable to complete urinary C-peptide measurement. Dotted line represents the published cutoff value for T1D ( 5 ). Error bars show mean and range.…”

Section: Resultsmentioning

confidence: 99%

“…Informed consent was obtained and documented in accordance with the institutional review boards at Vanderbilt University Medical Center and The University of Chicago. Participants underwent pancreas imaging using a standardized and validated MRI protocol developed as part of the MAP-T1D (Multicenter Assessment of the Pancreas in Type 1 Diabetes) program ( 4 ) as previously described ( 5 ). The pancreas volume (mL) was divided by the individual’s weight (kg) to yield the pancreas volume index (PVI).…”

Section: Methodsmentioning

confidence: 99%

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Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas

et al. 2023

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OBJECTIVE To determine the mechanism of reduced pancreas size in type 1 diabetes and the significance of islet-derived insulin in pancreatic growth. RESEARCH DESIGN AND METHODS Using a validated and standardized MRI protocol, we measured pancreas volume and shape in a family with an autosomal-dominant insulin gene mutation that results in insulin deficiency similar in severity to that of type 1 diabetes but without autoimmunity. DNA sequencing confirmed the mutation in all four affected individuals and none of the four control family members. Insulin secretory capacity was determined by measuring postprandial urinary C-peptide. RESULTS Family members with this form of monogenic diabetes had a markedly smaller pancreas and a severely impaired postprandial C-peptide level than family members without diabetes. CONCLUSIONS These results suggest that severe insulin deficiency, rather than islet-directed autoimmunity, leads to reduced pancreas size in type 1 diabetes and that insulin is a major trophic factor for the exocrine pancreas.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas

et al. 2023

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“…Moreover, 2-h OGTT requires a significant time commitment by both participants and staff, which also leads to high costs. On the other hand, a noncontrast pancreas MRI sufficient for quantifying pancreas volume can be acquired in 15 s. Thus, MRI screening can be performed at multiple sites and MRI machines if a standardized imaging protocol, such as the one we have developed, is used ( 18 ). Importantly, the movement toward shorter and less expensive MRI screening protocols in other organs such as the breast ( 29 ) demonstrates a potential pathway for reducing MRI cost and improving screening throughput through shorter scan times.…”

Section: Discussionmentioning

confidence: 99%

“…Pancreas MRI was performed using a Philips 3T Ingenia scanner (Vanderbilt and Chicago) or Siemens 3T Skyra scanner (Barbara Davis Center) according to a standardized protocol validated for quantitative pancreas evaluation across imaging centers and hardware ( 18 ). Imaging was performed at ∼6- or 12-month intervals, customarily aligning with OGTT, with additional MRI performed proximal to progression events.…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Assessment of Pancreas Volume by MRI Predicts Progression to Stage 3 Type 1 Diabetes

Virostko,

Wright,

Williams

et al. 2023

Diabetes Care

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OBJECTIVE This multicenter prospective cohort study compared pancreas volume as assessed by MRI, metabolic scores derived from oral glucose tolerance testing (OGTT), and a combination of pancreas volume and metabolic scores for predicting progression to stage 3 type 1 diabetes (T1D) in individuals with multiple diabetes-related autoantibodies. RESEARCH DESIGN AND METHODS Pancreas MRI was performed in 65 multiple autoantibody-positive participants enrolled in the Type 1 Diabetes TrialNet Pathway to Prevention study. Prediction of progression to stage 3 T1D was assessed using pancreas volume index (PVI), OGTT-derived Index60 score and Diabetes Prevention Trial–Type 1 Risk Score (DPTRS), and a combination of PVI and DPTRS. RESULTS PVI, Index60, and DPTRS were all significantly different at study entry in 11 individuals who subsequently experienced progression to stage 3 T1D compared with 54 participants who did not experience progression (P < 0.005). PVI did not correlate with metabolic testing across individual study participants. PVI declined longitudinally in the 11 individuals diagnosed with stage 3 T1D, whereas Index60 and DPTRS increased. The area under the receiver operating characteristic curve for predicting progression to stage 3 from measurements at study entry was 0.76 for PVI, 0.79 for Index60, 0.79 for DPTRS, and 0.91 for PVI plus DPTRS. CONCLUSIONS These findings suggest that measures of pancreas volume and metabolism reflect distinct components of risk for developing stage 3 type 1 diabetes and that a combination of these measures may provide superior prediction than either alone.

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“…All MRIs were conducted on BRI-consented subjects using 1.5 Tesla scanners located at Virginia Mason Medical Center. The MRI protocol consisted of a quantitative abdominal protocol previously validated for multisite reproducibility [ 25 ]. De-identified MRI data was shared with the University of Texas Austin for pancreas MRI analysis.…”

Section: Methodsmentioning

confidence: 99%

Testing a new platform to screen disease-modifying therapy in type 1 diabetes

Lord,

Bahnson,

Greenbaum

et al. 2023

PLoS ONE

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Studies of new therapies to preserve insulin secretion in early type 1 diabetes require several years to recruit eligible subjects and to see a treatment effect; thus, there is interest in alternative study designs to speed this process. Most people with longstanding type 1 diabetes no longer secrete insulin. However, studies from pancreata of those with longstanding T1D show that beta cells staining for insulin can persist for decades after diagnosis, and this is paralleled in work showing proinsulin secretion in individuals with longstanding disease; collectively this suggests that there is a reserve of alive but “sleeping” beta cells. Here, we designed a novel clinical trial platform to test whether a short course of therapy with an agent known to have effects in type 1 diabetes with residual endogenous insulin could transiently induce insulin secretion in those who no longer produce insulin. A therapy that transiently “wakes up” sleeping beta cells might be tested next in a fully powered trial in those with endogenous insulin secretion. In this three-arm non-randomized pilot study, we tested three therapies known to impact disease: two beta-cell supportive agents, liraglutide and verapamil, and an immunomodulatory agent, golimumab. The golimumab treated arm was not fully enrolled due to uncertainties about immunotherapy during the COVID-19 pandemic. Participants had mixed-meal tolerance test (MMTT)-stimulated C-peptide below the quantitation limit (<0.02 ng/mL) at enrollment and received 8 to 12 weeks of therapy. At the completion of therapy, none of the individuals achieved the primary outcome of MMTT-stimulated C-peptide ≥ 0.02 ng/mL. An exploratory outcome of the verapamil arm was MRI-assessed pancreas size, diffusion, and longitudinal relaxation time, which showed repeatability of these measures but no treatment effect. The liraglutide and golimumab arms were registered on clinicaltrials.gov under accession number NCT03632759 and the verapamil arm under accession number NCT05847413. Trail registration: Protocols are registered in ClinicalTrials.gov under accession numbers NCT03632759 and NCT05847413.

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Development of a standardized MRI protocol for pancreas assessment in humans

Cited by 11 publications

References 38 publications

Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas

Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas

Longitudinal Assessment of Pancreas Volume by MRI Predicts Progression to Stage 3 Type 1 Diabetes

Testing a new platform to screen disease-modifying therapy in type 1 diabetes

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