Compensatory Hippocampal Connectivity in Young Adults With Early-Stage Type 2 Diabetes.

CONTEXT: Middle-aged to elderly patients with type 2 diabetes mellitus (T2DM) exhibit reduced functional connectivity and brain atrophy underlying cognitive decrements; however, little is known about brain abnormalities in young patients. OBJECTIVE: To detect brain anatomical and functional changes in young patients with T2DM during the early disease stage. DESIGN: Case-control study. SETTING: Tertiary referral hospital. PARTICIPANTS: Thirty-five young patients with T2DM (<40 years of age) with no detectable microangiopathy and 32 nondiabetic control subjects. INTERVENTION: None. MAIN OUTCOME MEASURES: Subjects underwent neuropsychological assessments and structural and resting-state functional MRI. Both voxel-based morphometry and resting-state functional connectivity analyses were performed. RESULTS: No significant differences in brain volume were observed between the patients with T2DM and the controls after controlling for age, sex, education, and body mass index. Compared with the controls, the patients showed greater connectivity of the left hippocampus with the left inferior frontal gyrus and the left inferior parietal lobule. Moreover, the enhanced functional connectivity of left hippocampus with the left inferior frontal gyrus significantly correlated with disease severity (urinary albumin-to-creatinine ratio) (r = 0.613, P < 0.001) and executive function (completion time of Stroop Color and Word Test) (r = -0.461, P = 0.005) after false discovery rate correction. CONCLUSIONS: Our findings suggest an adaptive compensation of brain function to counteract the insidious cognitive decrements during the early stage of T2DM. Additionally, the functional alterations occurring before changes in brain structure and peripheral microangiopathy might serve as early biomarkers related to cognitive decrements.

Brain atrophy in middle-aged subjects with Type 2 diabetes mellitus, with and without microvascular complications.

BACKGROUND: The rapid rise in Type 2 diabetes mellitus (T2DM) among young adults makes it important to understand structural changes in the brain at a presenile stage. This study examined global and regional brain atrophy in middle-aged adults with T2DM, with a focus on those without clinical evidence of microvascular complications. METHODS: The study recruited 66 dementia-free middle-aged subjects (40 with T2DM, 26 healthy volunteers [HVs]). Patients were grouped according to the presence (T2DM-C; n = 20) or absence (T2DM-NC; n = 20) of diabetic microvascular complications. Global brain volume (including gray matter [GM] and white matter) was calculated based on voxel-based morphometry analysis. Regional GM volumes were further extracted using the anatomical automatic labeling template. RESULTS: There was a significant difference in global brain volume among groups (P = 0.003, anova). Global brain volume was lower in T2DM-C patients than in both T2DM-NC patients and HVs (mean [±SD] 0.720 ± 0.024 vs 0.736 ± 0.021 and 0.743 ± 0.019, respectively; P = 0.032 and P = 0.001, respectively). Regional analysis showed significant GM atrophy in the right Rolandic operculum (t = 3.42, P = 0.001) and right superior temporal gyrus (t = 2.803, P = 0.007) in T2DM-NC patients compared with age- and sex-matched HVs. CONCLUSIONS: Brain atrophy is present in dementia-free middle-aged adults with T2DM. Regional brain atrophy appears to be developing even in those with no clinical evidence of microvascular disturbances. The brain seems to be particularly vulnerable to metabolic disorders prior to peripheral microvascular pathologies associated with other target organs.

The value of magnetic resonance imaging in the detection of prostate cancer in patients with previous negative biopsies and elevated prostate-specific antigen levels: a meta-analysis.

RATIONALE AND OBJECTIVES: To assess the diagnostic performance of magnetic resonance imaging (MRI) for targeting prostate cancer in patients with previous negative biopsies and elevated prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: Pubmed, Scopus, and Cochrane Library databases were searched to identify suitable studies published from January 2001 to October 2013. Polled estimation and subgroup analysis data were obtained using a random effect model. Summary receiver operating characteristic curves were used to summarize overall test performance. RESULTS: Fourteen studies involving 698 patients met the included criteria. The mean prostate cancer detection rate was 37.5%. Twelve studies had a pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of 88%, 69%, and 16.84 by patient analysis, respectively. In the subgroup analysis, magnetic resonance imaging spectroscopy (MRSI) provided higher pooled sensitivity (91%) and specificity (69%) compared with T2-weighted imaging (T2WI). MRSI combined with MRI had the highest pooled specificity (73%). By site analysis, the pooled sensitivity, specificity, and DOR in nine studies were 57%, 90%, and 14.34, respectively. In the subgroup analysis, MRSI combined with MRI showed higher pooled sensitivity (58%) and specificity (93%) compared with T2WI. Diffusion-weighted MRI (DWI) showed the highest pooled specificity: 95% but the lowest pooled sensitivity: 38%. CONCLUSIONS: A limited number of studies suggest that the value of MRI to target prostate cancer in patients with previous negative biopsies and elevated PSA levels appears significant. MRI combined with MRSI is particularly accurate. Further studies are necessary to confirm the eventual role of DWI in this field.

In vivo MRI tracking of iron oxide nanoparticle-labeled human mesenchymal stem cells in limb ischemia.

BACKGROUND: Stem cell transplantation has been investigated for repairing damaged tissues in various injury models. Monitoring the safety and fate of transplanted cells using noninvasive methods is important to advance this technique into clinical applications. METHODS: In this study, lower-limb ischemia models were generated in nude mice by femoral artery ligation. As negative-contrast agents, positively charged magnetic iron oxide nanoparticles (aminopropyltriethoxysilane-coated Fe2O3) were investigated in terms of in vitro labeling efficiency, effects on human mesenchymal stromal cell (hMSC) proliferation, and in vivo magnetic resonance imaging (MRI) visualization. Ultimately, the mice were sacrificed for histological analysis three weeks after transplantation. RESULTS: With efficient labeling, aminopropyltriethoxysilane-modified magnetic iron oxide nanoparticles (APTS-MNPs) did not significantly affect hMSC proliferation. In vivo, APTS-MNP-labeled hMSCs could be monitored by clinical 3 Tesla MRI for at least three weeks. Histological examination detected numerous migrated Prussian blue-positive cells, which was consistent with the magnetic resonance images. Some migrated Prussian blue-positive cells were positive for mature endothelial cell markers of von Willebrand factor and anti-human proliferating cell nuclear antigen. In the test groups, Prussian blue-positive nanoparticles, which could not be found in other organs, were detected in the spleen. CONCLUSION: APTS-MNPs could efficiently label hMSCs, and clinical 3 Tesla MRI could monitor the labeled stem cells in vivo, which may provide a new approach for the in vivo monitoring of implanted cells.

Long-term MRI tracking of dual-labeled adipose-derived stem cells homing into mouse carotid artery injury.

BACKGROUND: Stem cell therapy has shown great promise for regenerative repair of injured or diseased tissues. Adipose-derived stem cells (ADSCs) have become increasingly attractive candidates for cellular therapy. Magnetic resonance imaging has been proven to be effective in tracking magnetic-labeled cells and evaluating their clinical relevance after cell transplantation. This study investigated the feasibility of imaging green fluorescent protein-expressing ADSCs (GFP-ADSCs) labeled with superparamagnetic iron oxide particles, and tracked them in vivo with noninvasive magnetic resonance imaging after cell transplantation in a model of mouse carotid artery injury. METHODS: GFP-ADSCs were isolated from the adipose tissues of GFP mice and labeled with superparamagnetic iron oxide particles. Intracellular stability, proliferation, and viability of the labeled cells were evaluated in vitro. Next, the cells were transplanted into a mouse carotid artery injury model. Clinical 3 T magnetic resonance imaging was performed immediately before and 1, 3, 7, 14, 21, and 30 days after cell transplantation. Prussian blue staining and histological analysis were performed 7 and 30 days after transplantation. RESULTS: GFP-ADSCs were found to be efficiently labeled with superparamagnetic iron oxide particles, with no effect on viability and proliferation. Homing of the labeled cells into the injured carotid artery tissue could be monitored by magnetic resonance imaging. CONCLUSION: Magnetically labeled ADSCs with expression of GFP can home into sites of vascular injury, and may provide new insights into understanding of cell-based therapy for cardiovascular lesions.

Studies of pathology and VEGF expression in rabbit cerebrospinal fluid metastasis: application of dynamic contrast-enhanced MRI.

OBJECTIVE: The objective was to analyze the correlation of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with vascular endothelial growth factor (VEGF) protein expression and to assess the potential application of DCE-MRI to the rabbit cerebrospinal fluid (CSF) metastasis model. METHODS: Thirty New Zealand rabbits were divided into experimental and control groups. In the experimental group, VX2 tumor cells were injected into the subarachnoid space at the plane of cisterna magna in 24 rabbits. In the control group, physiological saline was injected into the subarachnoid space at the plane of cisterna magna in six rabbits. DCE-MRI was performed at multiple time points, and several pharmacokinetic parameters, including K(trans), K(ep) and V(e), were calculated. Also, VEGF levels in plasma and CSF were evaluated by enzyme-linked immunosorbent assay prior to DCE-MRI examination. After DCE-MRI examination, the rabbits were sacrificed, and the corresponding tumor specimens were harvested. Hematoxylin-eosin staining and VEGF immunohistochemical staining were carried out, and VEGF expression in the specimens was evaluated by the immunohistochemical scoring system. RESULTS: Vascular endothelial growth factor positive staining was localized in the cytoplasm and cell membranes of tumor cells, as well as in a subset of epithelial cells. Both VEGF immunohistochemical scores and VEGF expression in CSF and plasma exhibited positive correlations with K(trans) and K(ep) values as demonstrated by rank correlation statistical analysis. CONCLUSIONS: Vascular endothelial growth factor expression in plasma and CSF in the CSF metastasis model was higher than in normal tissues. Therefore, DCE-MRI reliably indicated VEGF expression in the rabbit CSF metastasis model.

[MRI monitoring of cerebral spinal fluid metastasis in rabbit model].

OBJECTIVE: To establish a rabbit model of cerebral spinal flow metastasis, to analyze the growth rate of tumor, and to investigate the value of MRI in monitoring the biology of tumor compared with pathology. METHODS: Twenty-four New Zealand white rabbits were inoculated with suspension of VX(2) tumor cells in the subarachnoid space via the foramen magnum (experimental group), and 6 rabbits were inoculated with normal saline (control group). MRI examination, including non-enhanced T(1)WI, T(2)WI, and FLAIR sequences and then T(1)WI, FLAIR after dynamic contrast enhanced with Gd-DTPA were done 7 approximately 22 days after inoculation with a 3-day interval. The rabbits were killed after the last MRI scan with their spinal cords, spinal meninges, and tumor taken out to undergo microscopy. RESULTS: (1) MRI plain scan showed that in the experimental group 2 nodi in the medulla and 1 nodes in the cervical spinal cord were found with low signal on T(1)WI and high signal on T(2)WI; and FLAIR imaging showed local lesions with medial signal in 6 rabbits (25%). And no abnormal signs were seen in the control group. (2) MRI enhancement showed that in the experimental group the images of 15 rabbit models were enhanced markedly with irregular thickening of meninges or nodules at the subarachnoid space on T(1)WI, positive signs were confirmed on FLAIR sequence in 16 of the 24 rabbits, and positive signs were noted on DCE-MRI scanning in 18 of the 24 rabbits (75%). In the control group 5 of the 6 rabbits were negative in images. Microscopy showed thickened of meninges and spinal meninges in 20 of the 24 rabbits of the experimental group and spinal cord metastasis in 22 rabbits. No pathological changes were seen in the control group. Statistics showed a CSF metastasis rate of 91.67%. There were significant difference between the plain scan and T(1)WI with enhancement (P < 0.01) and between FLAIR scan and FLAIR enhancement scans. There was a significant difference between T(1)WI and FLAIR enhancement and pathological findings (P < 0.05). There was no significant difference between DCE-MRI method and pathological results (P > 0.05). CONCLUSION: Gd-DTPA enhanced MRI scan sequences has a high sensitivity and specificity and can be used in monitoring the growth of CSF metastasis. There is a disparity between the MRI signs and pathological findings. It is a key that to improve the spatial resolution of machine and to investigate the best method for detecting early metastasis.

[MRI monitoring ultra-small superparamagnetic iron oxide (USPIO) particle labeling C6 rat glioma cells].

OBJECTIVE: To monitor the effects of labeling C6 rat glioma cells with different concentrations of USPIO in vivo and in vitro. METHODS: C6 rat glioma cells of 1 x 10(6), 2 x 10(6) and 1 x 10(7) were labeled with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO, The signal intensity of cells were evaluated by MRI with T(1)WI, T(2)WI and GRE/30 degrees sequences in vitro. 1 x 10(6) of C6 glioma cells were labeled with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO and inoculated into the right frontal lobe of 2 rats under stereotaxis apparatus respectively (total 6 rats), Same MRI parameters were used just as above. Iron particle density and cells was measured by HE and Prussian blue stain under microscopy. RESULTS: Different cell population was cultured with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO about 12 hours. The MR signal intensity of labeling cells were inversely correlated with the different concentration of USPIO groups in T(2)W and GRE/30 degrees imaging (t = 4.19, 3.38, P < 0.05) in vitro. There was an inversely correlation between the labeling cell population and the signal intensity at the same concentration of USPIO (t = 5.16, 2.35, 4.41; P < 0.05). Dyeing degree of labeling cells stained by Prussian blue gradually deepened from 25 microg/ml to 50 microg/ml by microscopy. In vivo MRI can clearly show the cells labeled with 25 microg/ml USPIO. CONCLUSIONS: Iron particle density in the rat glioma cells were gradually increased with the concentration of USPIO. The MR signal intensity was inversely correlated with the cell population at the same condition. 25 microg/ml USPIO labeling rat glioma cells were enough for in vivo monitoring by MRI.