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High-resolution magnetic resonance imaging quantitatively detects individual pancreatic islets.

Lamprianou S, Immonen R, Nabuurs C, Gjinovci A, Vinet L, Montet XC, Gruetter R, Meda P - Diabetes (2011)

Bottom Line: In all cases, MR images were acquired in a 14.1 Tesla scanner and correlated with the corresponding (immuno)histological sections.MEHFMRI also detected a significant decrease in the numerical and volume density of islets in STZ-injected mice.However, in the latter measurements the loss of β-cells was undervalued under the conditions tested.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. smaragda.lamprianou@unige.ch

ABSTRACT

Objective: We studied whether manganese-enhanced high-field magnetic resonance (MR) imaging (MEHFMRI) could quantitatively detect individual islets in situ and in vivo and evaluate changes in a model of experimental diabetes.

Research design and methods: Whole pancreata from untreated (n = 3), MnCl(2) and glucose-injected mice (n = 6), and mice injected with either streptozotocin (STZ; n = 4) or citrate buffer (n = 4) were imaged ex vivo for unambiguous evaluation of islets. Exteriorized pancreata of MnCl(2) and glucose-injected mice (n = 6) were imaged in vivo to directly visualize the gland and minimize movements. In all cases, MR images were acquired in a 14.1 Tesla scanner and correlated with the corresponding (immuno)histological sections.

Results: In ex vivo experiments, MEHFMRI distinguished different pancreatic tissues and evaluated the relative abundance of islets in the pancreata of normoglycemic mice. MEHFMRI also detected a significant decrease in the numerical and volume density of islets in STZ-injected mice. However, in the latter measurements the loss of β-cells was undervalued under the conditions tested. The experiments on the externalized pancreata confirmed that MEHFMRI could visualize native individual islets in living, anesthetized mice.

Conclusions: Data show that MEHFMRI quantitatively visualizes individual islets in the intact mouse pancreas, both ex vivo and in vivo.

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Related in: MedlinePlus

MRI detects the loss of islets in a diabetic mouse model. A: High magnification MR and histology images of pancreas from mice injected with either CB (normoglycemic controls) or the buffer supplemented with STZ (hyperglycemic mice). Whitish (MRI)/pink islets (histology) were seen more frequently in the pancreata of control rather than of STZ-injected mice (some islets are pointed by green arrows). Scale bar: 1 mm and 0.5 mm in the insets. B: Morphometric analysis of the MR images showed that hyperglycemic mice had a pancreas volume (Vp; bottom) that was not significantly different from that of the citrate-injected controls. In contrast, the relative number (Nvi; top) and volume density (Vvi; middle) of the islets were decreased by 55 and 45%, respectively, in the STZ-injected mice. Data are mean + SEM of the indicated number of pancreas (**P < 0.01; *** P < 0.001). C: Immunostainings of consecutive pancreas sections of control and STZ-treated mice with antibodies against insulin and glucagon show that the STZ treatment significantly reduced the number of β-cells in most islets (outlined by white dotted lines). Most islets still contained many glucagon-containing α-cells. Some small islets (arrows) were essentially made by the latter type of islet cells and were fully devoid of insulin-containing cells. Scale bar: 0.5 mm. (A high-quality digital representation of this figure is available in the online issue.)
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Figure 4: MRI detects the loss of islets in a diabetic mouse model. A: High magnification MR and histology images of pancreas from mice injected with either CB (normoglycemic controls) or the buffer supplemented with STZ (hyperglycemic mice). Whitish (MRI)/pink islets (histology) were seen more frequently in the pancreata of control rather than of STZ-injected mice (some islets are pointed by green arrows). Scale bar: 1 mm and 0.5 mm in the insets. B: Morphometric analysis of the MR images showed that hyperglycemic mice had a pancreas volume (Vp; bottom) that was not significantly different from that of the citrate-injected controls. In contrast, the relative number (Nvi; top) and volume density (Vvi; middle) of the islets were decreased by 55 and 45%, respectively, in the STZ-injected mice. Data are mean + SEM of the indicated number of pancreas (**P < 0.01; *** P < 0.001). C: Immunostainings of consecutive pancreas sections of control and STZ-treated mice with antibodies against insulin and glucagon show that the STZ treatment significantly reduced the number of β-cells in most islets (outlined by white dotted lines). Most islets still contained many glucagon-containing α-cells. Some small islets (arrows) were essentially made by the latter type of islet cells and were fully devoid of insulin-containing cells. Scale bar: 0.5 mm. (A high-quality digital representation of this figure is available in the online issue.)

Mentions: To evaluate whether the loss of islets in an animal model of type 1 diabetes can be detected by MRI, we injected mice intraperitoneally with either 200 mg/kg b.w. STZ or an equivalent volume of the CB (sham treatment), which was used as vehicle for the drug (Fig. 4A). Two weeks after the STZ injections MRI evaluation showed that the hyperglycemic mice (Supplementary Table 1) had a pancreas volume (Vp; bottom panel of Fig. 4B) that was not significantly different from that of the citrate-injected controls. In contrast, the relative number (Nvi; top panel of Fig. 4B) and volume density (Vvi; middle panel of Fig. 4B) of the islets were decreased by 55% (P < 0.01) and 45% (P < 0.001), respectively, in the STZ-injected mice (Fig. 4B). These changes were confirmed by the histological analysis of the same pancreas (Fig. 4A). Given that the hyperglycemia of the STZ-injected mice (Supplementary Table 1) suggested a more profound drop of the insulin-producing β-cells, we immunostained the pancreas for insulin and glucagon (Fig. 4C). As expected, we found that the islets of the STZ-injected mice contained much less insulin-containing β-cells than those of controls. However, anti-glucagon staining demonstrated an increased number of glucagon-containing α-cells (Fig. 4C). In some cases, the latter cell type occupied almost the entire surface of the small, residual islets (Fig. 4C).


High-resolution magnetic resonance imaging quantitatively detects individual pancreatic islets.

Lamprianou S, Immonen R, Nabuurs C, Gjinovci A, Vinet L, Montet XC, Gruetter R, Meda P - Diabetes (2011)

MRI detects the loss of islets in a diabetic mouse model. A: High magnification MR and histology images of pancreas from mice injected with either CB (normoglycemic controls) or the buffer supplemented with STZ (hyperglycemic mice). Whitish (MRI)/pink islets (histology) were seen more frequently in the pancreata of control rather than of STZ-injected mice (some islets are pointed by green arrows). Scale bar: 1 mm and 0.5 mm in the insets. B: Morphometric analysis of the MR images showed that hyperglycemic mice had a pancreas volume (Vp; bottom) that was not significantly different from that of the citrate-injected controls. In contrast, the relative number (Nvi; top) and volume density (Vvi; middle) of the islets were decreased by 55 and 45%, respectively, in the STZ-injected mice. Data are mean + SEM of the indicated number of pancreas (**P < 0.01; *** P < 0.001). C: Immunostainings of consecutive pancreas sections of control and STZ-treated mice with antibodies against insulin and glucagon show that the STZ treatment significantly reduced the number of β-cells in most islets (outlined by white dotted lines). Most islets still contained many glucagon-containing α-cells. Some small islets (arrows) were essentially made by the latter type of islet cells and were fully devoid of insulin-containing cells. Scale bar: 0.5 mm. (A high-quality digital representation of this figure is available in the online issue.)
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Related In: Results  -  Collection

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Figure 4: MRI detects the loss of islets in a diabetic mouse model. A: High magnification MR and histology images of pancreas from mice injected with either CB (normoglycemic controls) or the buffer supplemented with STZ (hyperglycemic mice). Whitish (MRI)/pink islets (histology) were seen more frequently in the pancreata of control rather than of STZ-injected mice (some islets are pointed by green arrows). Scale bar: 1 mm and 0.5 mm in the insets. B: Morphometric analysis of the MR images showed that hyperglycemic mice had a pancreas volume (Vp; bottom) that was not significantly different from that of the citrate-injected controls. In contrast, the relative number (Nvi; top) and volume density (Vvi; middle) of the islets were decreased by 55 and 45%, respectively, in the STZ-injected mice. Data are mean + SEM of the indicated number of pancreas (**P < 0.01; *** P < 0.001). C: Immunostainings of consecutive pancreas sections of control and STZ-treated mice with antibodies against insulin and glucagon show that the STZ treatment significantly reduced the number of β-cells in most islets (outlined by white dotted lines). Most islets still contained many glucagon-containing α-cells. Some small islets (arrows) were essentially made by the latter type of islet cells and were fully devoid of insulin-containing cells. Scale bar: 0.5 mm. (A high-quality digital representation of this figure is available in the online issue.)
Mentions: To evaluate whether the loss of islets in an animal model of type 1 diabetes can be detected by MRI, we injected mice intraperitoneally with either 200 mg/kg b.w. STZ or an equivalent volume of the CB (sham treatment), which was used as vehicle for the drug (Fig. 4A). Two weeks after the STZ injections MRI evaluation showed that the hyperglycemic mice (Supplementary Table 1) had a pancreas volume (Vp; bottom panel of Fig. 4B) that was not significantly different from that of the citrate-injected controls. In contrast, the relative number (Nvi; top panel of Fig. 4B) and volume density (Vvi; middle panel of Fig. 4B) of the islets were decreased by 55% (P < 0.01) and 45% (P < 0.001), respectively, in the STZ-injected mice (Fig. 4B). These changes were confirmed by the histological analysis of the same pancreas (Fig. 4A). Given that the hyperglycemia of the STZ-injected mice (Supplementary Table 1) suggested a more profound drop of the insulin-producing β-cells, we immunostained the pancreas for insulin and glucagon (Fig. 4C). As expected, we found that the islets of the STZ-injected mice contained much less insulin-containing β-cells than those of controls. However, anti-glucagon staining demonstrated an increased number of glucagon-containing α-cells (Fig. 4C). In some cases, the latter cell type occupied almost the entire surface of the small, residual islets (Fig. 4C).

Bottom Line: In all cases, MR images were acquired in a 14.1 Tesla scanner and correlated with the corresponding (immuno)histological sections.MEHFMRI also detected a significant decrease in the numerical and volume density of islets in STZ-injected mice.However, in the latter measurements the loss of β-cells was undervalued under the conditions tested.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. smaragda.lamprianou@unige.ch

ABSTRACT

Objective: We studied whether manganese-enhanced high-field magnetic resonance (MR) imaging (MEHFMRI) could quantitatively detect individual islets in situ and in vivo and evaluate changes in a model of experimental diabetes.

Research design and methods: Whole pancreata from untreated (n = 3), MnCl(2) and glucose-injected mice (n = 6), and mice injected with either streptozotocin (STZ; n = 4) or citrate buffer (n = 4) were imaged ex vivo for unambiguous evaluation of islets. Exteriorized pancreata of MnCl(2) and glucose-injected mice (n = 6) were imaged in vivo to directly visualize the gland and minimize movements. In all cases, MR images were acquired in a 14.1 Tesla scanner and correlated with the corresponding (immuno)histological sections.

Results: In ex vivo experiments, MEHFMRI distinguished different pancreatic tissues and evaluated the relative abundance of islets in the pancreata of normoglycemic mice. MEHFMRI also detected a significant decrease in the numerical and volume density of islets in STZ-injected mice. However, in the latter measurements the loss of β-cells was undervalued under the conditions tested. The experiments on the externalized pancreata confirmed that MEHFMRI could visualize native individual islets in living, anesthetized mice.

Conclusions: Data show that MEHFMRI quantitatively visualizes individual islets in the intact mouse pancreas, both ex vivo and in vivo.

Show MeSH
Related in: MedlinePlus