Background:A major challenge to the development of biomarkers for pancreatic cancer (PC) is the small amount of tissue obtained at the time of diagnosis. Single-gene analyses may not reliably predict biology of PC because of its complex molecular makeup. MicroRNA (miRNA) profiling may provide a more informative molecular interrogation of tumours. The primary objective of this study was to determine the feasibility of performing miRNA arrays and quantitative real-time PCR (qRT–PCR) from archival formalin-fixed paraffin-embedded (FFPE) cell blocks obtained from fine-needle aspirates (FNAs) that is the commonest diagnostic procedure for suspected PC.Methods:MicroRNA expression profiling was performed on FFPE from FNA of suspicious pancreatic masses. Subjects included those who had a pathological diagnosis of pancreatic adenocarcinoma and others with a non-malignant pancreatic histology. Exiqon assay was used to quantify miRNA levels and qRT–PCR was used to validate abnormal expression of selected miRNAs.Results:A total of 29 and 15 subjects had pancreatic adenocarcinoma and no evidence of cancer, respectively. The RNA yields per patient varied from 25 to 100 ng. Profiling demonstrated deregulation of over 228 miRNAs in pancreatic adenocarcinoma of which the top 7 were further validated by qRT–PCR. The expression of let-7c, let-7 f, and miR-200c were significantly reduced in most patients whereas the expression of miR-486-5p and miR-451 were significantly elevated in all pancreas cancer patients. MicroRNAs let-7d and miR-423-5p was either downregulated or upregulated with a significant inter-individual variation in their expression.Conclusion:This study demonstrated the feasibility of using archival FFPE cell blocks from FNAs to establish RNA-based molecular signatures unique to pancreatic adenocarcinoma with potential applications in clinical trials for risk stratification, patient selection, and target validation.
HighlightsTo date, there is no standard MR imaging protocol to characterize the nigrosome1 territory of the substantia nigra.Nigrosome 1 can be consistently visualized using true SWI with a resolution of at least 0.67 × 0.67 × 1.34 mm3.Loss of nigrosome 1 on true SWI can differentiate Parkinsonism from healthy controls.Not all 'Parkinson's disease patients show bilateral loss of nigrosome 1.
Background
To determine if extracranial venous structural and flow abnormalities exist in patients with multiple sclerosis (MS).
Methods
Magnetic resonance imaging was used to assess the anatomy and function of major veins in the neck in 138 MS patients and 67 healthy controls (HC). Time-of-flight (TOF) MR angiography (MRA) was used to assess stenosis while 2D phase contrast flow quantification (PCFQ) was used to assess flow at the C2/C3 and C5/C6 levels. Venous flow was normalized to the total arterial flow. The MS patients were divided into stenotic and non-stenotic groups based on MRA assessment, and each group was compared to the HC group in anatomy and flow.
Results
The MS group showed lower normalized internal jugular vein (IJV) blood flow (tIJV/tA) than the HC group (p < 0.001). In the MS group, 72 (52%) evidenced stenosis (ST) while 66 (48%) were non-stenotic (NST). In the HC group, 11 (23%) showed a stenosis while 37 (77%) were non-stenotic. The ST-MS group had lower IJV flow than both HC and NST-MS groups.
Conclusion
After categorizing the MS population into two groups based upon anatomical stenosis determined from an absolute quantification of IJV cross-section, clear differences in IJV flow between the stenotic MS and HC samples became evident. Despite the unknown etiology of MS, abnormal venous flow was noted in a distinct group of MS patients compared to HC.
Background:
Iron is important in the pathophysiology of Parkinson’s disease (PD) specifically related to degeneration of the substantia nigra (SN). Magnetic resonance imaging (MRI) can be used to measure brain iron in the entire structure but this approach is insensitive to regional changes in iron content.
Objective:
The goal of this work was to use quantitative susceptibility mapping (QSM) and R2
∗
to quantify both global and regional brain iron in PD patients and healthy controls (HC) to ascertain if regional changes correlate with clinical conditions and can be used to discriminate patients from controls.
Methods:
Susceptibility and R2
∗
maps of 25 PD and 24 HC subjects were reconstructed from data collected on a 3T GE scanner. For the susceptibility maps, three-dimensional regions-of-interest (ROIs) were traced on eight deep gray matter (DGM) structures and an age-based threshold was applied to define regions of high iron content. The same multi-slice ROIs were duplicated on the R2
∗
maps as well. Mean susceptibility values of both global and regional high iron (RII) content along with global R2
∗
values were measured and compared not only between the two cohorts, but also to susceptibility and R2
∗
baselines as a function of age. Finally, clinical features were compared for those PD patients lying above and below the upper 95% regional susceptibility-age prediction intervals.
Results:
The SN was the only structure showing significantly higher susceptibility in PD patients compared to controls globally (
p
< 0.01) and regionally (
p
< 0.001). The R2
∗
values were also higher only in the SN of PD patients compared to the healthy cohort (
p
< 0.05). Furthermore, those patients with abnormal susceptibility values lying above the upper 95% prediction intervals had significantly higher united Parkinson’s diagnostic rating scores. R2
∗
values had larger errors and showed larger dispersion as a function of age than QSM data for global analysis while the dispersion was significantly less for QSM using the RII iron content.
Conclusion:
Abnormal iron deposition in the SN, especially in RII areas, could serve as a biomarker to distinguish PD patients from HC and to assess disease severity.
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