Purpose To evaluate the role of magnetization transfer (MT) magnetic resonance (MR) imaging for the characterization of intestinal fibrosis compared with contrast material-enhanced and ...diffusion-weighted MR imaging and its capability for differentiating fibrotic from inflammatory strictures in humans with Crohn disease (CD) by using surgical histopathologic analysis as the reference standard. Materials and Methods Institutional review board approval and informed consent were obtained for this prospective study. Abdominal MT imaging, contrast-enhanced imaging, and diffusion-weighted imaging of 31 consecutive patients with CD were analyzed before elective surgery. The bowel wall MT ratio normalized to skeletal muscle, the apparent diffusion coefficient (ADC), and the percentage of enhancement gain were calculated; region-by-region correlations with the surgical specimen were performed to determine the histologic degree of fibrosis and inflammation. The performance of MT imaging was validated in five new patients. One-way analysis of variance test, Spearman rank correlation, and receiver operating characteristic curve were used for statistical analysis. Results Normalized MT ratios strongly correlated with fibrosis scores (r = 0.769; P = .000) but did not correlate with inflammation scores (r = -0.034; P = .740). Significant differences (F = 49.002; P = .000) in normalized MT ratios were found among nonfibrotic, mildly, moderately, and severely fibrotic walls. The normalized MT ratios of mixed fibrotic and inflammatory bowel walls were significantly higher than those of bowel walls with only inflammation present (t = -8.52; P = .000). A high accuracy of normalized MT ratios was shown with an area under the receiver operating characteristic curve (AUC) of 0.919 (P = .000) for differentiating moderately to severely fibrotic bowel walls from nonfibrotic and mildly fibrotic bowel walls, followed by ADC (AUC, 0.747; P = .001) and the percentage of enhancement gain (AUC, 0.592; P = .209). The sensitivity, specificity, and AUC of MT imaging for diagnosing moderate to severe fibrosis in the validation data set were 80% (12 of 15), 100% (three of three), and 0.9 (P = .033), respectively. Conclusion MT imaging outperforms ADC and contrast-enhanced imaging in detecting and distinguishing varying degrees of bowel fibrosis with or without coexisting inflammation. MT imaging could potentially be used as a method to differentiate fibrotic from inflammatory intestinal strictures in patients with CD.
RSNA, 2018 Online supplemental material is available for this article.
Objectives
Identifying inflammation- or fibrosis-predominant strictures in Crohn’s disease (CD) is crucial for treatment strategies. We evaluated the additive value of magnetisation transfer (MT) to ...conventional MRI for differentiating CD strictures using surgical histopathology as a reference standard.
Methods
Twenty-eight consecutive CD patients who underwent MRI preoperatively were recruited. MRI parameters included T2-weighted imaging (T2WI) hyperintensity, bowel wall thickness, enhancement pattern changes over time, enhancement pattern and gain ratio in dynamic contrast-enhanced phases, and MT ratio. Correlation analysis was performed using Spearman’s rank test. Receiver operating characteristic curve analysis and Cohen’s
κ
were used. A model with combined MRI variables characterising intestinal strictures was proposed and validated in 14 additional CD patients.
Results
Significant correlations with histological inflammation scores were shown for wall thickness (
r
= 0.361,
p
= 0.001) and T2WI hyperintensity (
r
= 0.396,
p
< 0.001), whereas histological fibrosis scores were significantly correlated with MT ratio (
r
= 0.681,
p
< 0.001) and wall thickness (
r
= 0.461,
p
< 0.001). T2WI hyperintensity could differentiate mild from moderate-to-severe inflammation with a sensitivity of 0.871 and a specificity of 0.800. MT ratio could discriminate mild from moderate-to-severe fibrosis with a sensitivity and a specificity of 0.913 and 0.923, respectively. Combining MT ratio and T2WI hyperintensity, the MRI classification moderately agreed with the pathological stricture classification (
p
< 0.01,
κ
= 0.549). In the validation set, the diagnostic accuracy of T2WI hyperintensity and MT ratio were 86% and 89%, with good agreement between MRI and histopathological classification (
p
< 0.01,
κ
= 0.665).
Conclusions
MT ratio combined with conventional MRI improves the differentiation of fibrotic from inflammatory components of small-bowel strictures in CD patients.
Key Points
• MT ratio from magnetisation transfer imaging combined with T2WI from conventional MRI can simultaneously characterise bowel fibrosis and inflammation in adult Crohn’s disease
.
BACKGROUND
Assessing bowel fibrosis in patients with Crohn's disease (CD) has important therapeutic implications.
PURPOSE
To determine the utility of T2* mapping versus that of contrast enhanced (CE) ...imaging in grading intestinal fibrosis in patients with CD using surgical pathology as the reference standard.
STUDY TYPE
Prospective.
SPECIMENS
102 specimens from 27 patients with CD.
FIELD STRENGTH/SEQUENCE
3.0T; T2WI; T1WI; T2*WI.
ASSESSMENT
The T2*WI values of the bowel wall targeted for resection were measured by two radiologists by drawing regions of interest on the thickened bowel wall. The resected bowel specimens with pathological fibrosis and type I collagen were classified into four severity grades (0–3) by a pathologist using a semi‐quantitative scoring system.
STATISTICAL TESTS
The differences in the T2*WI values among the different histological grades were analyzed using one‐way analysis of variance or the Kruskal‐Wallis test, and their correlations were analyzed. The ability of the T2*WI values to discriminate between various degrees of fibrosis was assessed using a receiver operating characteristic (ROC) curve.
RESULTS
Significant differences were observed in the T2* values of mild (23.56 ± 1.60 ms), moderate (16.19 ± 0.55 ms), and severe (13.59 ± 0.53 ms) fibrosis types (F = 35.84; P < 0.001). T2* values were moderately associated with histological fibrosis (r = ‐0.627; P < 0.001) and type I collagen scores (r = ‐0.588; P < 0.001). T2* values were highly accurate, with an area under the ROC curve (AUC) of 0.951 (P < 0.001) for differentiating moderate‐to‐severe fibrosis from nonfibrosis and mild fibrosis, followed by an AUC of 0.508 for the percentage of enhancement gain (P = 0.908). A threshold T2* value of 18.06 ms was recommended for diagnosing moderate‐to‐severe fibrosis with 94.7% sensitivity and 78.3% specificity.
DATA CONCLUSION
MRI T2* mapping outperforms CE parameters in distinction of various degrees of bowel fibrosis in CD.
Level of Evidence: 1
Technical Efficacy: Stage 2
J. Magn. Reson. Imaging 2018;48:829–836.
Objectives
Intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) provides information on both perfusion and diffusion and has been used to evaluate Crohn’s disease ...(CD) activity and fibrosis in children; however, there are no reports on its use in adults. We aimed to determine its value for detecting and grading intestinal fibrosis in adults with CD compared with contrast-enhanced imaging and traditional diffusion-weighted imaging using surgical histopathology as a reference standard.
Methods
Twenty-four adults with CD underwent preoperative IVIM, traditional diffusion-weighted, and contrast-enhanced imaging. Region-by-region correlations between MRI findings and histologic findings of the surgical specimens were performed. Imaging parameters including fractional perfusion, perfusion coefficient, and diffusion coefficient for IVIM and apparent diffusion coefficient value for traditional diffusion-weighted imaging and contrast-enhanced parameter of 95 bowel lesions were measured. Intestinal fibrosis was histologically scored from 0 to 3.
Results
The fractional perfusion (
r
= − 0.629,
p
< 0.001) and apparent diffusion coefficient values (
r
= − 0.495,
p
< 0.001) were significantly correlated with fibrosis scores. Fractional perfusion decreased following increases in fibrosis severity from mild, to moderate, to severe (
p
< 0.001). The area under the receiver operating characteristic curve for distinguishing moderate-severe from mild fibrosis was 0.876 (
p
< 0.001) for fractional perfusion, followed by 0.802 for apparent diffusion coefficient value (
p
< 0.001). Perfusion coefficient, diffusion coefficient, and contrast-enhanced parameter were uncorrelated with histological fibrosis.
Conclusions
IVIM diffusion-weighted magnetic resonance imaging outperforms traditional diffusion-weighted and contrast-enhanced imaging in grading bowel fibrosis, and fractional perfusion may be a promising biomarker for fibrosis severity in adults with CD.
Key Points
•
Intravoxel incoherent motion diffusion-weighted MRI outperforms contrast-enhanced imaging and traditional diffusion-weighted MRI for detecting and grading intestinal fibrosis in adult Crohn’s disease.
•
The parameter fractional perfusion, a promising biomarker for fibrosis severity, may be beneficial for treatment planning and monitoring of bowel fibrosis in adult Crohn’s disease.
•
Perfusion coefficient, diffusion coefficient, and the percentage of enhancement gain between 70 s and 7 min were uncorrelated with histological fibrosis.
Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn's disease CD. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has ...seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index MCFI based on computed tomography CT in CD patients.
MCFI was developed based on vascular findings on CT in a retrospective cohort n = 91 and validated in a prospective cohort n = 30. The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score.
In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate-severe from mild fibrostenosis (area under the receiver operating characteristic ROC curve AUC = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of > 3 which accurately differentiated fibrostenosis severity in the prospective cohort AUC = 0.756; p = 0.018. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort r = 0.840, p = 0.000. Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis.
MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.
Objectives
Although diffusion-weighted imaging (DWI) is reported to be accurate in detecting bowel inflammation in Crohn’s disease (CD), its ability to assess bowel fibrosis remains unclear. This ...study assessed the role of DWI in the characterization of bowel fibrosis using surgical histopathology as the reference standard.
Methods
Abdominal DWI was performed before elective surgery in 30 consecutive patients with CD. The apparent diffusion coefficients (ADCs) in pathologic bowel walls were calculated. Region-by-region correlations between DWI and the surgical specimens were performed to determine the histologic degrees of bowel fibrosis and inflammation.
Results
ADCs correlated negatively with bowel inflammation (
r
= − 0.499,
p
< 0.001) and fibrosis (
r
= − 0.464,
p
< 0.001) in 90 specimens; the ADCs in regions of nonfibrosis and mild fibrosis were significantly higher than those in regions of moderate–severe fibrosis (
p =
0.008). However, there was a significant correlation between the ADCs and bowel fibrosis (
r
= − 0.641,
p
= 0.001) in mildly inflamed segments but not in moderately (
r
= − 0.274,
p
= 0.255) or severely (
r
= − 0.225,
p
= 0.120) inflamed segments. In the mildly inflamed segments, the ADCs had good accuracy with an area under the receiver-operating characteristic curve of 0.867 (
p
= 0.004) for distinguishing nonfibrosis and mild fibrosis from moderate–severe fibrosis.
Conclusions
ADC can be used to assess bowel inflammation in patients with CD. However, it only enables the accurate detection of the degree of bowel fibrosis in mildly inflamed bowel walls. Therefore, caution is advised when using ADC to predict the degree of intestinal fibrosis.
Key Points
• Diffusion-weighted imaging was used to assess bowel inflammation in patients with Crohn’s disease.
• The ability of diffusion-weighted imaging to evaluate bowel fibrosis decreased with increasing bowel inflammation.
• Diffusion-weighted imaging enabled accurate detection of the degree of fibrosis only in mildly inflamed bowel walls.
Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with ...pathogenesis of Alzheimer’s disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.
This study was investigated to utilize innovatively oil-free diaphragm pump to forcibly desorb the hydrogen from the small pilot MgH2–TiH2 based hydride reactor below the theoretical temperature of ...278 °C. Active MgH2-0.1TiH2 composites were prepared using ball milling. Their hydrogenation performances at 25–300 °C were measured under a constant H2 flow mode using a modified Sieverts apparatus. The dehydrogenation rates at 250–350 °C with or without diaphragm pump were investigated to examine whether the pilot reactors could be integrated with a proton exchange membrane fuel cell (PEMFC) for power generation. At a H2 flow rate of 25 ml min−1 g−1, the reactors exhibited excellent hydrogenation, achieving gravimetric hydrogen storage capacities of 2.9–5.2 wt% (excluding the weight of the reactors) at 25–300 °C after 22 min. All hydrided MgTi–based reactors could be dehydrogenated at 250 °C at an average rate of 5 ml min−1 g−1 under vacuum. This is the first demonstration of Mg-based reactors that were hydrogenated at 100 °C and dehydrogenated at 250 °C to power a small PEMFC, yielding a measured conversion efficiency of 18%.
Display omitted
•A small reactor containing active MgTi–based hydrides was developed.•The reactors readily absorbed 2.9 wt%−5.2 wt% H2 at 25 C−300 °C in 22 min.•H2 flows desorbed from the reactors at 250 °C via a diaphragm pump successfully powered PEMFCs.
Depression is among the most frequent psychiatric comorbid conditions in Alzheimer disease (AD). However, pharmacotherapy for depressive disorders in AD is still a big challenge, and the data on the ...efffcacy of current antidepressants used clinically for depressive symptoms in patients with AD remain inconclusive. Here we investigated the mechanism of the interactions between depression and AD, which we believe would aid in the development of pharmacological therapeutics for the comorbidity of depression and AD. Female APP/PS1/Tau triple transgenic (3×Tg-AD) mice at 24 months of age and age- and sex-matched wild-type (WT) mice were used. The shuttle-box passive avoidance test (PAT) were implemented to assess the abilities of learning and memory, and the open field test (OFT) and the tail suspension test (TST) were used to assess depression-like behavior. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to detect the level of neurotransmitters related to depression in the hippocampus of mice. The data was identified by orthogonal projections to latent structures discriminant analysis (OPLS-DA). Most neurotransmitters exert their effects by binding to the corresponding receptor, so the expression of relative receptors in the hippocampus of mice was detected using Western blot. Compared to WT mice, 3×Tg-AD mice displayed significant cognitive impairment in the PAT and depression-like behavior in the OFT and TST. They also showed significant decreases in the levels of L-tyrosine, norepinephrine, vanillylmandelic acid, 5-hydroxytryptamine, and acetylcholine, in contrast to significant increases in 5-hydroxyindoleacetic acid, L-histidine, L-glutamine, and L-arginine in the hippocampus. Moreover, the expression of the alpha 1a adrenergic receptor (ADRA1A), serotonin 1 A receptor (5HT1A), and γ-aminobutyric acid A receptor subunit alpha-2 (GABRA2) was significantly downregulated in the hippocampus of 3×Tg-AD mice, while histamine H3 receptor (H3R) expression was significantly upregulated. In addition, the ratio of phosphorylated cAMP-response element-binding protein (pCREB) and CREB was significantly decreased in the hippocampus of 3×Tg-AD mice than WT mice. We demonstrated in the present study that aged female 3×Tg-AD mice showed depression-like behavior accompanied with cognitive dysfunction. The complex and diverse mechanism appears not only relevant to the imbalance of multiple neurotransmitter pathways, including the transmitters and receptors of the monoaminergic, GABAergic, histaminergic, and cholinergic systems, but also related to the changes in L-arginine and CREB signaling molecules.
A validated histopathological tool to precisely evaluate bowel fibrosis in patients with Crohn's disease is lacking. We attempted to establish a new index to quantify the severity of bowel fibrosis ...in patients with Crohn's disease-associated fibrostenosis.
We analyzed the histopathological data of 31 patients with Crohn's disease strictures undergoing surgical resection. The most representative sections of resected strictured segments were stained with Masson trichrome to manifest bowel fibrosis. The collagen area fraction and histological fibrosis score were simultaneously calculated for the same section to evaluate the severity of bowel fibrosis.
Collagen area fraction strongly correlated with histological fibrosis scores (r = 0.733, P < 0.001). It showed a stronger correlation (r = 0.561, P < 0.001) with the degree of bowel strictures than the histological fibrosis score did (r = 0.468, P < 0.001). It was also shown to be more accurate for diagnosing Crohn's disease strictures (area under the receiver operating characteristic curve = 0.815, P < 0.001) compared with the histological fibrosis score (area under the curve = 0.771, P < 0.001). High repeatability was observed for the collagen area fraction, with an intraclass correlation coefficient of 0.915 (P < 0.001).
Collagen area fraction is a simple and reliable index to quantify the severity of bowel fibrosis in patients with Crohn's disease-associated fibrostenosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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