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Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type 1 diabetes progression in preclinical models.

ABSTRACT: In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and ?-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and ?-cell decline would allow the diagnosis of eventual diabetes, and provide a means to monitor therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a denser microvasculature that reorganizes during diabetes. Here we apply contrast-enhanced ultrasound measurements of pancreatic blood-flow dynamics to non-invasively and predictively assess disease progression in T1D pre-clinical models. STZ-treated mice, NOD mice, and adoptive-transfer mice demonstrate altered islet blood-flow dynamics prior to diabetes onset, consistent with islet microvasculature reorganization. These assessments predict both time to diabetes onset and future responders to antiCD4-mediated disease prevention. Thus contrast-enhanced ultrasound measurements of pancreas blood-flow dynamics may provide a clinically deployable predictive marker for disease progression in pre-symptomatic T1D and therapeutic reversal.

SUBMITTER: St Clair JR

PROVIDER: S-EPMC5931596 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type 1 diabetes progression in preclinical models.

St Clair Joshua R JR Ramirez David D Passman Samantha S Benninger Richard K P RKP

Nature communications 20180501 1

In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and β-cell decline would allow the diagnosis of eventual diabetes, and provide a means to monitor therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a denser microvasculatur ...[more]

PMID: 29717116

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Project description:New findingsWhat is the central question of this study? Contrast-enhanced ultrasound (CEUS) can be used to directly assess skeletal muscle perfusion but its day-to-day repeatability over time has not yet been validated: is CEUS a repeatable method for the measurement of skeletal muscle microvascular blood flow (MBF) at rest and in response to exercise, across independent assessment sessions? What is the main finding and its importance? A strong agreement between CEUS MBF measures across sessions suggests it is a repeatable method for assessing skeletal muscle perfusion over time. This validation provides confidence for incorporating these measures into longitudinal studies such as a chronic intervention or disease progression to gain further knowledge of skeletal muscle microvascular function.AbstractContrast-enhanced ultrasound (CEUS) can be used to directly assess skeletal muscle perfusion. However, its repeatability over time has not yet been validated and therefore its use in longitudinal measures (i.e., exploring the impact of a chronic intervention or disease progression) is limited. This study aimed to determine the repeatability of CEUS for the measurement of skeletal muscle microvascular blood flow (MBF) at baseline and in response to exercise, across independent assessment sessions. Ten healthy volunteers (five female; 30 ± 6 years) had CEUS of the right vastus lateralis recorded in two separate sessions, 14 days apart. Measurements were taken at baseline, during an isometric leg extension and during recovery. Acoustic intensity data from a region of interest were plotted as a replenishment curve to obtain blood volume (A) and flow velocity (β) values from a one-phase association non-linear regression of mean tissue echogenicity. Linear regression and Bland-Altman analyses of A and β values were performed, with significance assumed as P < 0.05. Strong positive correlations were observed across sessions for all A and β values (both P < 0.0001). Bland-Altman analysis showed a bias (SD) of -0.013 ± 1.24 for A and -0.014 ± 0.31 for β. A bias of 0.201 ± 0.770 at baseline, 0.527 ± 1.29 during contraction and -0.203 ± 1.29 at recovery was observed for A, and -0.0328 ± 0.0853 (baseline), -0.0446 ± 0.206 (contraction) and 0.0382 ± 0.233 (recovery) for β. A strong agreement between CEUS MBF measures across independent sessions suggests it to be a repeatable method for assessing skeletal muscle perfusion over time, and therefore facilitates wider use in longitudinal studies.

Project description:BackgroundThe aim of modern medicine is to safely classify diseases for successful therapy without invasive measures. Sonography, computed tomography (CT), and magnetic resonance imaging (MRI) are potent imaging techniques. However, without contrast medium, the informative value of the 3 native methods is limited. The advantages of sonography are: no radiation exposure or previously known physically harmful interactions with tissue, proportionate disappearance of a contrast agent risk, no (probably irreversible) contrast agent deposits, and no risk of renal insufficiency. But, is that enough to compete with of even exceed CT and MRI?SummaryIn this review, the state of the art of contrast-enhanced ultrasound (CEUS) in the abdominal cavity is presented. The remarkable diagnostic possibilities can unfortunately only be demonstrated here in a small number of impressive, typical case studies underpinned by the literature, so that, from one's own perspective, the full spectrum of CEUS can be used by oneself or initiated. Within the limits of physics, the real-time dynamics of CEUS enable conclusions to be drawn, so that with the current technology, sonography, including expansion by contrast, can be considered superior to other imaging methods. It is not uncommon for CEUS to have the value of a control and reference method.Key messagesSonography very often enables reliable diagnostics. The introduction of a contrast agent in sonography has led to a quantum leap similar to that of other imaging techniques. Already natively, the real-time representation of dynamic events leads to a certain superiority, i.e., complete observation of the inflow and outflow phases of the contrast medium and the resulting diagnostic; tissue-specific differentiation options provide a unique selling point. Further advantages of the first-choice imaging diagnostic method are: a lack of radiation exposure, repeatability of the examination at any time, local independence, a negligible allergy rate compared to the contrast agents of other methods, and a lack of kidney and thyroid exposure or excluded deposits.

Project description:Background Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

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Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type 1 diabetes progression in preclinical models.

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Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type 1 diabetes progression in preclinical models.

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