In vivo MRI virtual colonography in a mouse model of colon cancer.
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ABSTRACT:
SUBMITTER: Ileva LV
PROVIDER: S-EPMC8381262 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Early detection of precancerous tissue has significantly improved survival of most cancers including colorectal cancer (CRC). Animal models designed to study the early stages of cancer are valuable for identifying molecular events and response indicators that correlate with the onset of disease. The goal of this work was to investigate magnetic resonance (MR) colonography in a mouse model of CRC on a clinical MR imager. Mice treated with azoxymethane and dextran sulfate sodium were imaged by serial MR colonography (MRC) from initiation to euthanasia. Magnetic resonance colonography was obtained with both T1- and T2-weighted images after administration of a Fluorinert enema to remove residual luminal signal and intravenous contrast to enhance the colon wall. Individual tumor volumes were calculated and validated ex vivo. The Fluorinert enema provided a clear differentiation of the lumen of the colon from the mucosal lining. Inflammation was detected 3 days after dextran sulfate sodium exposure and subsided during the next week. Tumors as small as 1.2 mm(3) were detected and as early as 29 days after initiation. Individual tumor growths were followed over time, and tumor volumes were measured by MR imaging correlated with volumes measured ex vivo. The use of a Fluorinert enema during MRC in mice is critical for differentiating mural processes from intraluminal debris. Magnetic resonance colonography with Fluorinert enema and intravenous contrast enhancement will be useful in the study of the initial stages of colon cancer and will reduce the number of animals needed for preclinical trials of prevention or intervention.
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Project description:Texture features have played an essential role in the field of medical imaging for computer-aided diagnosis. The gray-level co-occurrence matrix (GLCM)-based texture descriptor has emerged to become one of the most successful feature sets for these applications. This study aims to increase the potential of these features by introducing multi-scale analysis into the construction of GLCM texture descriptor. In this study, we first introduce a new parameter - stride, to explore the definition of GLCM. Then we propose three multi-scaling GLCM models according to its three parameters, (1) learning model by multiple displacements, (2) learning model by multiple strides (LMS), and (3) learning model by multiple angles. These models increase the texture information by introducing more texture patterns and mitigate direction sparsity and dense sampling problems presented in the traditional Haralick model. To further analyze the three parameters, we test the three models by performing classification on a dataset of 63 large polyp masses obtained from computed tomography colonoscopy consisting of 32 adenocarcinomas and 31 benign adenomas. Finally, the proposed methods are compared to several typical GLCM-texture descriptors and one deep learning model. LMS obtains the highest performance and enhances the prediction power to 0.9450 with standard deviation 0.0285 by area under the curve of receiver operating characteristics score which is a significant improvement.
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Project description:ObjectiveThe purpose of the present study is to evaluate the diagnostic performance of and interreader agreement for CT colonography (CTC) in the local staging of colon cancer, with emphasis given to the FOxTROT (Fluoropyrimidine, Oxaliplatin, and Targeted-Receptor pre-Operative Therapy [Panitumumab]) trial inclusion criteria, which propose a new tailored treatment paradigm for colon cancer that uses neoadjuvant therapy for patients with a high-risk of locoregional disease as determined by imaging.Materials and methodsThis biinstitutional retrospective study involved 89 patients (with 93 tumors) who had colon cancer and underwent presurgical CTC. Two radiologists reviewed the CTC studies for local staging, including measurement of the tumor beyond the muscularis propria on a true orthogonal plane. Histopathologic findings for surgical colectomy specimens served as the reference standard for local pathologic staging. The sensitivity, specificity, positive predictive value, and negative predictive value for local determination of the T category, N category, and extramural vascular invasion (EMVI) were calculated separately for each reader. High-risk T category tumors were the same as those as used in the FOxTROT trial. Interreader agreement was assessed using the kappa statistic.ResultsThirty-five of 93 tumors (37.6%) were histologically classified as high-risk tumors (T3c, T3d, or T4 tumors). The interreader agreement was substantial (? = 0.68) for classifying high-risk tumors with the use of CTC, moderate for differentiating N0 from N1 and N2 (? = 0.44), and slight for detecting EMVI (? = 0.15). The diagnostic statistics for CTC for the two readers were as follows: for detection of high-risk tumors, sensitivity was 65.7% and 82.9%, and specificity was 81.0% and 87.9%; for detection of N category-positive disease, sensitivity was 50.9% and 69.8%, and specificity was 50.0% and 72.5%; and for detection of EMVI, sensitivity was 18.2% and 66.7%, and specificity was 60.0% and 91.7%.ConclusionThe present study shows that CTC might be a feasible imaging modality for preoperative local staging of higher-risk colon cancers for which neoadjuvant chemotherapy is more suitable on the basis of the FOxTROT trial criteria. However, further studies are required to allow a better generalization of our results.
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Project description:Periventricular leukomalacia, PVL, is the leading cause of cerebral palsy in prematurely born infants, and therefore more effective interventions are required. The objective of this study was to develop an ischemic injury model of PVL in mice and to determine the feasibility of in vivo magnetization transfer (MT) magnetic resonance imaging (MRI) as a potential monitoring tool for the evaluation of disease severity and experimental therapeutics. Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal day 5 (P5); at P60, in vivo T2-weighted (T2w) and MT-MRI were performed and correlated with postmortem histopathology. In vivo T2w MRI showed thinning of the right corpus callosum, but no significant changes in hippocampal and hemispheric volumes. Magnetization transfer MRI revealed significant white matter abnormalities in the bilateral corpus callosum and internal capsule. These quantitative MT-MRI changes correlated highly with postmortem findings of reduced myelin basic protein in bilateral white matter tracts. Ventriculomegaly and persistent astrogliosis were observed on the ligated side, along with evidence of axonopathy and fewer oligodendrocytes in the corpus callosum. We present an ischemia-induced mouse model of PVL, which has pathologic abnormalities resembling autopsy reports in infants with PVL. We further validate in vivo MRI techniques as quantitative monitoring tools that highly correlate with postmortem histopathology.
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Project description:Hypoxia-inducible factor 1α (HIF1α) is a transcription factor that regulates the adaptation of cells to hypoxic microenvironments, for example inside solid tumours. Stabilisation of HIF1α can also occur in normoxic conditions in inflamed tissue or as a result of inactivating mutations in negative regulators of HIF1α. Aberrant overexpression of HIF1α in many different cancers has led to intensive efforts to develop HIF1α-targeted therapies. However, the role of HIF1α is still poorly understood in chronic inflammation that predisposes the colon to carcinogenesis. We have previously reported that the transcription of HIF1α is upregulated and that the protein is stabilised in inflammatory lesions that are caused by the non-steroidal anti-inflammatory drug (NSAID) sulindac in the mouse proximal colon. Here, we exploited this side effect of long-term sulindac administration to analyse the role of HIF1α in colon inflammation using mice with a Villin-Cre-induced deletion of Hif1α exon 2 in the intestinal epithelium (Hif1α(ΔIEC)). We also analysed the effect of sulindac sulfide on the aryl hydrocarbon receptor (AHR) pathway in vitro in colon cancer cells. Most sulindac-treated mice developed visible lesions, resembling the appearance of flat adenomas in the human colon, surrounded by macroscopically normal mucosa. Hif1α(ΔIEC) mice still developed lesions but they were smaller than in the Hif1α-floxed siblings (Hif1α(F/F)). Microscopically, Hif1α(ΔIEC) mice had significantly less severe colon inflammation than Hif1α(F/F) mice. Molecular analysis showed reduced MIF expression and increased E-cadherin mRNA expression in the colon of sulindac-treated Hif1α(ΔIEC) mice. However, immunohistochemistry analysis revealed a defect of E-cadherin protein expression in sulindac-treated Hif1α(ΔIEC) mice. Sulindac sulfide treatment in vitro upregulated Hif1α, c-JUN and IL8 expression through the AHR pathway. Taken together, HIF1α expression augments inflammation in the proximal colon of sulindac-treated mice, and AHR activation by sulindac might lead to the reduction of E-cadherin protein levels through the mitogen-activated protein kinase (MAPK) pathway.
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Project description:Although synbiotics may be effective in maintaining remission of inflammatory bowel disease, their anticarcinogenic effects are still debated. To address this issue, we evaluated the effects of synbiotics, probiotics, and prebiotics on tumorigenesis using a CDX2P-Cre; Apc+/flox mouse model harboring a colon-specific Apc knock out, which develops adenoma and adenocarcinoma of the colon. Dextran sodium sulfate (DSS)-administration promoted colonic tumor development in CDX2P-Cre; Apc+/flox mice, and these tumors were associated with loss of Apc heterozygosity, as confirmed by observation of well-differentiated adenocarcinomas with β-catenin accumulation in tumor cell cytoplasm. Synbiotics-treatment suppressed dextran sodium sulfate-induced colitis in CDX2P-Cre; Apc+/flox mice, thereby reducing mortality, and inhibited tumorigenesis accelerated by DSS-administration. Conversely, neither probiotics nor prebiotics had any effect on inflammation and tumorigenesis. Lactobacillus casei and Bifidobacterium breve were detected in the fecal microbiota of probiotics-treated mice. Synbiotics-treatment suppressed DSS-induced expression of IL-6, STAT-3, COX-2, and TNF-α gene transcripts in normal colonic epithelium, indicating the possibility of suppressing tumor development. Importantly, these genes may be potential therapeutic targets in inflammation-associated colon cancer.
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Project description:With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our "in-skull" preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes.
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Project description:AimsThe mdx mouse has proven to be useful in understanding the cardiomyopathy that frequently occurs in muscular dystrophy patients. Here we employed a comprehensive array of clinically relevant in vivo MRI techniques to identify early markers of cardiac dysfunction and follow disease progression in the hearts of mdx mice.Methods and resultsSerial measurements of cardiac morphology and function were made in the same group of mdx mice and controls (housed in a non-SPF facility) using MRI at 1, 3, 6, 9 and 12 months after birth. Left ventricular (LV) and right ventricular (RV) systolic and diastolic function, response to dobutamine stress and myocardial fibrosis were assessed. RV dysfunction preceded LV dysfunction, with RV end systolic volumes increased and RV ejection fractions reduced at 3 months of age. LV ejection fractions were reduced at 12 months, compared with controls. An abnormal response to dobutamine stress was identified in the RV of mdx mice as early as 1 month. Late-gadolinium-enhanced MRI identified increased levels of myocardial fibrosis in 6, 9 and 12-month-old mdx mice, the extent of fibrosis correlating with the degree of cardiac remodeling and hypertrophy.ConclusionsMRI could identify cardiac abnormalities in the RV of mdx mice as young as 1 month, and detected myocardial fibrosis at 6 months. We believe these to be the earliest MRI measurements of cardiac function reported for any mice, and the first use of late-gadolinium-enhancement in a mouse model of congenital cardiomyopathy. These techniques offer a sensitive and clinically relevant in vivo method for assessment of cardiomyopathy caused by muscular dystrophy and other diseases.
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Project description:BackgroundThe Chinese Society of Clinical Oncology guidelines 2018 and the recent update of that (version 2020) recommends accurate examination before major treatment for decision(s) in cases of colon cancer. Also, the difficulty in the identification of the lesion during colectomy may lead to resection of a wrong segment of the colon or a more extensive resection than planned. Accurate pre-colectomy local staging of colon cancer is required to make decisions for treatment of colon cancer. The objective of the study was to evaluate the diagnostic performance of the computed tomography colonography (CTC) for pre-colectomy tumor location and tumor, node, and metastasis (TNM) staging of colon cancer.MethodsData of preoperative colonoscopies, CTC, surgeries, and surgical pathology of a total of 269 patients diagnosed with colon cancer by colonoscopy and biopsy and underwent pre-colectomy location and TNM staging by CTC were collected and analyzed. The consistency between the radiological and the surgery/surgical-pathological for location and TN stages of colon tumor were estimated with the weighted kappa or kappa coefficient (κ) at 95% confidence interval (CI).ResultsCTC detected 261 (93%) and colonoscopy detected 201 (72%) correct locations of tumors. Sensitivity and accuracy of CTC for detection of location of colon tumors were 100% and 92.58% (κ = 0.89; 95% Cl: 0.83-0.95). 72.48% sensitivity, 90.64% specificity, and 83.57% accuracy were reported for CTC in differentiation of tumors confined to the colon wall (T1/T2) from advanced tumors (T3/T4) (κ = 0.69, 95% Cl: 0.51-0.75). 81.01% sensitivity, 89.11% specificity, and 83.93% accuracy of CTC was reported for differentiation of tumors between low-intermediate risk and high risk (κ = 0.68, 95% Cl: 0.53-0.75). 69.31% sensitivity, 66.15% specificity, and 67.14% accuracy of CTC were reported for N staging of tumors (κ = 0.41, 95% Cl: 0.59-0.69).ConclusionsCTC has high diagnostic parameters for pre-colectomy location and T staging of colon tumors except patients of colon cancer who received neoadjuvant chemotherapy.Level of evidenceIII.Technical efficacy stage2.
| S-EPMC8051039 | biostudies-literature