Imaging of Aging Pancreas

The non-invasive imaging of the endocrine pancreas is currently considered by concerned institutions as a priority theme of research. Because the endocrine pancreas represents only about one percent of the pancreatic gland, highly specific tools are required for labelling the insulin-producing cells. The present review deals with the possible use of D-mannoheptulose for the non-invasive quantification of insulin-producing cells in the pancreas. This heptose is transported into hepatocytes and insulin-producing cells, but not other cell types, at the intervention of GLUT2. Its uptake coincides with the intracellular accumulation of acidic metabolites generated by phosphorylation of D-mannoheptulose. These metabolites remain in the islet cells after prolonged washing, suggesting that imaging of the pancreas at a relatively late time after intravenous administration of D-mannoheptulose could avoid significant extracellular contamination. Using tritiated D-mannoheptulose as tracer, a new method was designed for quantification of the total mass of insulin-producing cells in either isolated perfused rat pancreata or isolated pancreatic islets. Likewise, a preferential labelling of hepatocytes and insulin-producing transplanted cells can be achieved in vivo after administration of tritiated D-mannoheptulose. In the light of results obtained with 6-deoxy-6-iodo-D-glucose, it is proposed that 7-deoxy-7-iodo-D-mannoheptulose could be used for the non-invasive imaging of the endocrine pancreas.

Pancreas is a small organ approximately six inches long, located at upper abdomen and adjacent to the small intestine. It is located at the back and deep into the human body. Therefore, it difficult to obtain a pancreas image clearly using ultrasound machine. In order to solve this problem, MATLAB software was used to filter and segment the ultrasound pancreas images using various methods. The images were selected based on high quality images produced from five subjects using AplioMX device from Toshiba ultrasound machine with a 3.5MHz convex transducer. In this study, there were various technique of filter used including Kaun filter, Wiener filter, Frost filter and Anisotropic Diffusion filter in order to reduce spackle noise of ultrasound pancreas images. Then, the filtered images were measured using Mean Square Error (MSE), Power Signal to Noise Ratio (PSNR), Average Difference (AD), Normalized Cross-Correlation (NCC), Maximum Difference (MD), Structural Content (SC), and Normalized Absolute Error (NAE) formula to evaluate the best quality images before undergo the segmentation process. As the result, Wiener filter was selected. In the segmentation process, the active countor method and level set method were evaluated. Then, the area of binary image and error percentage were calculated. As a conclusion, it shows that the filtering process using Wiener filter and segmentation method using level sets method has been successfully done to produce the best geometry of pancreas image.

Magnetic resonance imaging (MRI) has detected changes in pancreas volume and other characteristics in type 1 and type 2 diabetes. However, differences in MRI technology and approaches across locations currently limit the incorporation of pancreas imaging into multisite trials. The purpose of this study was to develop a standardized MRI protocol for pancreas imaging and to define the reproducibility of these measurements. Calibrated phantoms with known MRI properties were imaged at five sites with differing MRI hardware and software to develop a harmonized MRI imaging protocol. Subsequently, five healthy volunteers underwent MRI at four sites using the harmonized protocol to assess pancreas size, shape, apparent diffusion coefficient (ADC), longitudinal relaxation time (T1), magnetization transfer ratio (MTR), and pancreas and hepatic fat fraction. Following harmonization, pancreas size, surface area to volume ratio, diffusion, and longitudinal relaxation time were reproducible, with coefficients of variation less than 10%. In contrast, non-standardized image processing led to greater variation in MRI measurements. By using a standardized MRI image acquisition and processing protocol, quantitative MRI of the pancreas performed at multiple locations can be incorporated into clinical trials comparing pancreas imaging measures and metabolic state in individuals with type 1 or type 2 diabetes.

Amylase‐creatinine clearance ratio and radionuclide hepatobiliary and pancreas imaging were used together as noninvasive screening procedures in 24 patients suspected of having acute pancreatitis. An increased amylase‐creatinine clearance ratio, normal filling of the gallbladder demonstrated by the radionuclide study, and decreased uptake of the radionuclide in the pancreas scan were helpful in reaching the diagnosis of acute pancreatitis.

Magnetic resonance imaging (MRI) has detected changes in pancreas volume and other characteristics in type 1 and type 2 diabetes. However, differences in MRI technology and approaches across locations currently limit the incorporation of pancreas imaging into multisite trials. The purpose of this study was to develop a standardized MRI protocol for pancreas imaging and to define the reproducibility of these measurements. Calibrated phantoms with known MRI properties were imaged at five sites with differing MRI hardware and software to develop a harmonized MRI imaging protocol. Subsequently, five healthy volunteers underwent MRI at four sites using the harmonized protocol to assess pancreas size, shape, apparent diffusion coefficient (ADC), longitudinal relaxation time (T1), magnetization transfer ratio (MTR), and pancreas and hepatic fat fraction. Following harmonization, pancreas size, surface area to volume ratio, diffusion, and longitudinal relaxation time were reproducible, with coefficients of variation less than 10%. In contrast, non-standardized image processing led to greater variation in MRI measurements. By using a standardized MRI image acquisition and processing protocol, quantitative MRI of the pancreas performed at multiple locations can be incorporated into clinical trials comparing pancreas imaging measures and metabolic state in individuals with type 1 or type 2 diabetes.

The physiology and pathophysiology of the pancreas are complex. Diseases of the pancreas, such as pancreatitis and pancreatic adenocarcinoma (PDAC) have high morbidity and mortality. Intravital imaging (IVI) is a powerful technique enabling the high-resolution imaging of tissues in both healthy and diseased states, allowing for real-time observation of cell dynamics. IVI of the murine pancreas presents significant challenges due to the deep visceral and compliant nature of the organ, which make it highly prone to damage and motion artifacts. Described here is the process of implantation of the Stabilized Window for Intravital imaging of the murine Pancreas (SWIP). The SWIP allows IVI of the murine pancreas in normal healthy states, during the transformation from the healthy pancreas to acute pancreatitis induced by cerulein, and in malignant states such as pancreatic tumors. In conjunction with genetically labeled cells or the administration of fluorescent dyes, the SWIP enables the measurement of single-cell and subcellular dynamics (including single-cell and collective migration) as well as serial imaging of the same region of interest over multiple days. The ability to capture tumor cell migration is of particular importance as the primary cause of cancer-related mortality in PDAC is the overwhelming metastatic burden. Understanding the physiological dynamics of metastasis in PDAC is a critical unmet need and crucial for improving patient prognosis. Overall, the SWIP provides improved imaging stability and expands the application of IVI in the healthy pancreas and malignant pancreas diseases.

To explore the stability and repeatability of diffusion-weighted imaging (DWI) of normal pancreas with different field of views (FOV) on 5.0 T magnetic resonance imaging (MRI) system. Twenty healthy subjects underwent two sessions of large FOV (lFOV) and reduced FOV (rFOV) DWI sequence scanning. Two radiologists measured the apparent diffusion coefficient (ADC) values and the signal-to-noise ratio (SNR) of the pancreatic head, body, and tail on DWI images, simultaneously, using a 5-point scale, evaluate the artifacts and image quality. One radiologist re-measured the ADC on DWI images again after a 4-week interval. The test-retest repeatability of two scan sessions were also evaluated. Intra-observer and inter-observer at lFOV and rFOV, the ADC values were not significantly different (P > 0.05), intraclass correlation coefficients (ICCs) and coefficient of variations were excellence (ICCs 0.85–0.99, CVs < 8.0%). The ADC values were lower with rFOV than lFOV DWI for the head, body, tail, and overall pancreas. The consistency of the two scan sessions were high. The high stability and repeatability of pancreas DWI has been confirmed at 5.0 T. Scan durations are reduced while resolution and image quality are improved with rFOV DWI, which is more preferable than lFOV for routine pancreas imaging.

Featuring more than 300 high-quality radiographs and scan images, clinical imaging of the pancreas systematically reviews all appropriate imaging modalities for diagnosing and evaluating a variety of commonly encountered pancreatic disorders. After presenting a succinct overview of pancreatic embryology, anatomy, and physiology, the authors establish the clinical indications-including postoperative patient evaluation-for radiologic examination of the pancreas. The diagnostic capabilities and limitations of currently available imaging techniques for the pancreas are thoroughly assessed, with carefully selected illustrations depicting the types of images and data obtained using these different techniques. The review of acute and chronic pancreatitis considers the clinical features and possible complications of their variant forms and offers guidance in selecting appropriate imaging studies.

The possible use of a mouse monoclonal antibody directed against rat pancreatic B-cell surface ganglioside(s) and labelled with radioactive iodine for selective imaging of the endocrine pancreas by a non-invasive procedure was investigated by following its pancreatic fate in experiments conducted either in vitro by incubation of rat isolated pancreatic islets, acinar tissue and pancreatic pieces or in vivo after intravenous injection of the (125)I-labelled antibodies ([(125)I]gamma-G). Although the binding of [(125)I]gamma-G per microg protein was about one order of magnitude higher in isolated islets than in acinar tissue, no significant difference was detected when comparing pancreatic pieces or isolated islets from control animals and rats rendered diabetic by one or two prior administrations of streptozotocin (STZ rats). Likewise, except in one set of experiments, no significant difference was found between control animals and STZ rats, when measuring the radioactive content of the pancreatic gland, relative to that of plasma, 1-4 days after the intravenous injection of [(125)I]gamma-G. These findings indicate that under the present experimental conditions, the mouse monoclonal antibody labelled with radioactive iodine does not appear to be a promising tool for selective imaging of the endocrine pancreas, e.g. by single photon emission computerized tomography.

Prior to ultrasonic B-scanning, imaging of the pancreas had been both difficult and lacking in diagnostic accuracy. Conventional radiology, including barium studies, and radionuclide imaging of the pancreas are often suboptimal. The diagnostic accuracy of selective angiography is approximately 80 percent. Furthermore, this is an invasive procedure with definite incidences of patient morbidity, precluding its use as a screening procedure.

The imaging and quantification of the endocrine pancreas by a non-invasive procedure remains a challenge. In the prolongation of prior work on selected succinic acid esters and monosaccharide esters, it is proposed that D-mannoheptulose, which might be transported across the plasma membrane at the intervention of GLUT-2, could be used to label preferentially the endocrine moiety of the pancreatic gland. This heptose is taken up more efficiently by hepatocytes and islet cells, than by erythrocytes, parotid cells, acinar pancreatic cells or tumoural islet cells of either the RINm5F or INS-1 line. Likewise, D-mannoheptulose only inhibits D-glucose metabolism in hepatocytes and isolated islets. Its hexaacetate ester, however, inhibits the catabolism of the hexose in all cell types. The uptake of D-mannoheptulose represents a carrier-mediated process. Human islets behave like rat islets in terms of D-mannoheptulose uptake and inhibition by the heptose of both D-glucose metabolism and insulinotropic action. The use of radiolabelled analogs of D-mannoheptulose suitable for imaging of the endocrine pancreas is discussed. In the same perspective, it is proposed that advantage could be taken of the much greater accumulation of glycogen in insulin-producing cells, as compared to other pancreatic cell types, in situations of sustained hyperglycaemia.

To evaluate differences in apparent diffusion coefficient (ADC) values between head, body, and tail regions and the impact of sets of b-values used in diffusion weighted imaging (DWI) of the normal pancreas. In 51 healthy volunteers echo-planar DWI of the pancreas was prospectively performed with b-values of 50, 400, and 800 s/mm(2) . All four possible combinations of b-values were used to calculate ADC values in a total of 587 regions in the pancreas head, body, and tail regions. Dependency of ADC values on the anatomical regions and on the applied sets of b-values was calculated using multivariate analysis of variance (ANOVA). Mean ADC values differed significantly between the anatomical regions with the lowest values measured in the pancreatic tail (head 1.13 ± 0.20, body 1.05 ± 0.20, and tail 0.94 ± 0.18 × 10(-3) mm(2) /s; P < 0.05). ANOVA showed no dependency of ADC values on the sets of b-values used. ADC values differed significantly between the pancreatic head, body, and tail region, with decreasing ADC values toward the tail. Cautious interpretation of DWI results with adjusted, normalized values adapted to the anatomical region seems advisable. The knowledge of such differences may enhance the method's capability to differentiate between different pancreatic pathologies.

6-[(18)F]fluoro-L-3,4-dihydroxyphenyl alanine ([(18)F]FDOPA) positron emission tomography (PET) is a diagnostic tool which can detect malignancies of the pancreas. We aimed to study whether the manipulation of the [(18)F]FDOPA metabolic pathway would change the (18)F-behavior to provide a biochemical foundation for PET imaging of rat pancreas with [(18)F]FDOPA. Inhibitors of aromatic amino acid decarboxylase, catechol-O-methyltransferase, monoamine oxidases A and B, or their combinations on [(18)F]FDOPA uptake, metabolism, and the regional distribution in the rat pancreas was evaluated using in vivo PET/computed tomography imaging, chromatographic metabolite analyses, and autoradiography. Enzyme inhibition generally increased the uptake of [(18)F]FDOPA derived (18)F-radioactivity in rat pancreas. Dependent on which enzymatic pathway is blocked (or a combination of pathways), different radiolabeled metabolites in pancreas are responsible for this increase in uptake. Altering the metabolism of [(18)F]FDOPA by using various enzymatic inhibitors increased the radioactivity uptake and changed the radiometabolic profile in the pancreas allowing better discrimination between pancreas and surrounding tissues of rat. However, these manipulations did not separate islets from the exocrine pancreas. Elucidating the metabolic behavior of [(18)F]FDOPA provides a biochemical foundation of PET imaging of the rat pancreas.

Time-course magnetic resonance imaging of rat pancreatic cyst after experimental pancreatitis

Diabetes is characterized by impaired insulin production by pancreatic beta cells. Metabolic testing in clinical settings does not adequately reflect beta cell mass (BCM), which is a target of multiple therapies under development. Thus, reliable imaging agents are needed for monitoring changes in beta cells during diabetes development and therapy. Various imaging modalities such as PET/CT, SPECT, MRI and PET-MRI have been investigated for in vivo imaging of pancreas. Application of these modalities for beta cell imaging is hampered by lack of beta cell specific imaging probes. Proteomics, systems biology, antibody library screening and phage display screening have been employed to find a suitable target on beta cell surface in order to design the probes for imaging functional beta cell mass. We expect that in the near future these methods will eventually lead to discovery of suitable marker(s) for beta cell paving the way for development of imaging probes for clinical settings. Keywords: Antibody, beta-cells, chromatography, diabetes, imaging, IC2 MRI, proteomics, targetsphingomyelin, target, sphingomyelin