An ultra-metastatic model of human colon cancer in nude mice

An ultra-high metastatic model of human colon cancer was developed in order to represent highly malignant patient disease for which there is no current model. Surgical orthotopic implantation (SOI) of a histologically intact liver metastasis fragment derived from a surgical specimen of a patient with metastatic colon cancer was initially implanted in the colon, liver and subcutaneously in nude mice. This tumor did not metastasize for the first 10 passages. At the eleventh passage, the tumor exhibited metastasis from the colon to the liver, spleen, and lymph nodes. At this time, two selective passages were carried out by transplanting resulting liver metastases in the nude mice to the colon of additional nude mice. After these two passages, the tumor became stably ultra-metastatic and was termed AC3488UM. One-hundred percent of mice transplanted with AC3488UM with SOI to the colon exhibited local growth, regional invasion, and spontaneous metastasis to the liver, lymph nodes, and spleen. While the maximum size of the primary tumor was 0.9 g, the metastatic liver was over 9 times the weight of the normal liver with the maximum weight of the metastatic liver over 12 g. Liver metastases were detected by the tenth day after transplantation in all animals. Half the animals died of metastatic tumor 25 days after transplantation. Histological characteristics of AC3488UM tumor were poorly differentiated adenocarcinoma of colon. Mutant p53 is expressed heterogeneously in the primary tumor and more homogeneously in the liver metastasis suggesting a possible role of p53 in the liver metastasis. The human origin of AC3488UM was confirmed by positive fluorescence staining for in situ hybridization of human DNA. The AC3488 human colon-tumor model with its ultra-high metastatic capability in each transplanted animal, short latency and a short median survival period is different from any known human colon cancer model and will be an important tool for the study of and development of new therapy for highly metastatic human colon cancer.     

Establishment of lymph node metastatic model for human gastric cancer in nude mice and analysis of factors associated with metastasis

The actual mechanisms responsible for lymph node metastasis in gastric cancer are still unclear. To investigate the mechanisms of lymph node metastasis in gastric cancer, we established a lymph node metastatic model for human scirrhous gastric carcinoma. Lymph node metastasis had frequently developed after orthotopic implantation of OCUM-2M LN derived from a scirrhous gastric cancer cell line, OCUM-2M, which had low capacity for lymph node metastasis. We elucidated the different characteristics including binding ability, migratory capacity and immunoresponses induced by the cell surface molecules of these two cell lines. The binding ability to Matrigel and migratory capacity of OCUM-2M LN cells were significantly greater than those of OCUM-2M cells. On flow cytometric analysis, both OCUM-2M and OCUM-2M LN cells strongly expressed HLA-I (99.5 and 97.1%) and LFA-3 (76.6 and 99.2%) in level of expression between the two cell lines, but neither cell line expressed HLA-II (0.0 and 0 .0%), B7-1 (0.0 and 0.0%) or B7-2 (0.4 and 0.3%). ICAM-1 expression in OCUM-2M LN cells was weaker (0.7%) than that in OCUM-2M cells (36.8%). Strong adhesiveness and cytotoxicity of mononuclear lymphocytes for OCUM-2M cells were observed in adhesion and cytotoxic assays, both of which were significantly decreased by the addition of anti-ICAM-1 antibodies. On the other hand, the adhesiveness and cytotoxicity of OCUM-2M LN cells were significantly less than those of OCUM-2M cells, and were not affected by the addition of anti-ICAM-1 antibodies. These findings suggest that decreased ICAM-1 expression in a new gastric cancer cell line with a high rate of lymph node metasta-sis may in turn decrease immune responses mediated through LFA-1-dependent effector cell adhesion, and that this escape from the immunosurveillance system may be one of the factors inducing lymph node metas-tasis. In conclusion, we established a gastric cancer cell line, OCUM-2M LN, with a high rate of lymph node metasta sis. An in vivo lymph node-metastatic model with this cell line should be useful for analysing the mech-anism and therapeutic approach of lymph node metastasis. © Rapid Science Ltd.     

Development of a high metastatic orthotopic model of human renal cell carcinoma in nude mice: benefits of fragment implantation compared to cell-suspension injection

In this study we compared the metastatic rate of human renal cell carcinoma SN12C in two orthotopic nude mouse models: surgical orthotopic implantation (SOI) of histologically intact tumor tissue and cellular orthotopic injection (COI) of cell suspensions in the kidney. The primary tumors resulting from SOI were larger and much more locally invasive than primary tumors resulting from COI. SOI generated higher metastatic expression than COI. The differences in metastatic rates in the involved organs (lung, liver, and mediastinal lymph nodes) were 2–3 fold higher in SOI compared to COI (P<0.05). Median survival time in the SOI model was 40 days, which was significantly shorter than that of COI (68 days) (P<0.001). Histological observation of the primary tumors from the SOI model demonstrated a much richer vascular network than the COI model. Lymph node and lung metastases were larger and more cellular in the SOI model compared to COI. We conclude that the tissue architecture of the implanted tumor tissue in the SOI model plays an important role in the initiation of primary tumor growth, invasion, and distant metastasis. This study directly demonstrates that the implantation of histologically intact tumor tissue orthotopically allows accurate expression of the clinical features of human renal cancer in nude mice. This model should be of value in cancer research and antimetastatic drug discovery for renal cancer, a currently very poorly responding malignancy.     

Peritoneal metastatic model for human scirrhous gastric carcinoma in nude mice

We established a peritoneal-metastatic model for scirrhous gastric carcinoma. Peritoneal metastasis had developed after intraperitoneal inoculation of OCUM-2MD3 cells in nude mice. This cell line was derived from a peritoneal-metastatic nodule at the mesenterium after orthotopic implantation of OCUM-2M cells which developed no peritoneal metastasis after intraperitoneal inoculation. The histologic findings of orthotopic-implanted tumor in the stomach show scirrhous type while those of subcutaneous-implanted tumor show medullary type. There might be factors, in OCUM-2MD3 cells, which are responsible for peritoneal metastasis. We next investigated the differences in the biological behavior of the original OCUM-2M and the derived variant OCUM-2MD3. Morphology and growth activity of the two cell lines were similar to each other. The specific chromosomes, add(6)(g13), del(7)(q21.2) and inv(11)(pl3q21), were found in OCUM-2MD3 cells but not in OCUM-2M cells. While the oncogenes amplification by OCUM-2M cells was found in K-sam and c-myc, that by OCUM-2MD3 cells was found only in c-myc. The expression of E-cadherin by OCUM-2MD3 cells was decreased compared with that of OCUM-2M cells. Expression level of β1-integrin of OCUM-2MD3 cells was higher than that of OCUM-2M cells. The binding and invasion activity of OCUM-2MD3 cells were higher than those of OCUM-2M cells, and were decreased by anti-β1-integrin antibody. The invasion activity of OCUM-2MD3 cells was increased in the presence of peritoneal fibroblast. In this study, it was suggested that orthotopic implantation of cancer cells might have an effect on the acquisition of metastatic ability. β1-integrin and peritoneal fibroblasts might be correlated with peritoneal metastasis. This peritoneal-metastatic model should be useful for analysing the mechanism of peritoneal metastasis of human scirrhous gastric cancer.     

Antimetastatic efficacy of adjuvant gemcitabine in a pancreatic cancer orthotopic model

Gemcitabine is a promising new agent that has been recently studied for palliation of advanced (stage IV) unresectable pancreatic cancer. We hypothesized that adjuvant gemcitabine would reduce recurrence and metastases following surgical resection of pancreatic cancer. To test this hypothesis, we evaluated gemcitabine on a green fluorescent protein (GFP) transductant of the human pancreatic cancer cell line BxPC-3 (BxPC-3-GFP) using surgical orthotopic implantation (SOI) in nude mice. GFP enabled high resolution fluorescent visualization of primary and metastatic growth. Five weeks after SOI, the mice were randomized into three groups: Group I received exploratory laparotomy only. Group II underwent surgical resection of the pancreatic tumor without further treatment. Group III underwent tumor resection followed by adjuvant treatment with gemcitabine, 100 mg/kg every three days for a total of four doses, starting two days after resection. The mice were sacrificed at thirteen weeks following implantation and the presence and location of recurrent tumor was recorded. Gemcitabine reduced the recurrence rate to 28.6% compared to 70.6% with resection only (P=0.02) and reduced metastatic events 58% in the adjuvant group compared to resection only. This study, demonstrating that gemcitabine is effective as adjuvant chemotherapy post-pancreatectomy, suggests this new indication of the drug clinically. This revised version was published online in July 2006 with corrections to the Cover Date.     

A fluorescent orthotopic model of metastatic cervical carcinoma

Currently, there is no mouse model of cervical cancer that allows for the study of the later stages of the disease, including metastasis. We report here the development of an orthotopic model of human cervical carcinoma in which tumor fragments are surgically implanted into the cervix of SCID mice. The human cervical carcinoma cell lines used in this study (CaSki, ME-180, and SiHa) have been engineered to stably express the fluorescent proteins enhanced green fluorescent protein (EGFP) or DsRed2, allowing for in vivo optical monitoring of tumor growth and metastasis. The cervical implants develop into large intraperitoneal masses involving the entire reproductive tract, with little local invasion of other abdominal structures. These tumors metastasize initially to local lymph nodes and later to lung, a pattern consistent with the clinical course of the disease. It was found that the use of the DsRed2 protein as a fluorescent marker has distinct advantages over EGFP due to the wavelength of its emission spectrum (575-625 nm vs 500-550 nm). Tissue penetration of light at this wavelength is greater, and the auto-fluorescence of mouse tissues is less intense, resulting in an enhanced signal to noise ratio compared to results obtained with EGFP. This model should allow for a more relevant investigation of the factors that affect the metastasis of cervical carcinoma and presents an opportunity to evaluate potential therapeutic strategies designed to prevent the spread of disease.     

Magnetic resonance imaging of the human cervix: a study of the effects of prostaglandins in the first trimester

BACKGROUND: To establish that magnetic resonance imaging (MRI) can provide an objective measurement of the biophysical state of the cervix and to measure the response of the cervix to prostaglandins in the first trimester of pregnancy. METHODS: A comparative study, with each patient serving as her own control, was carried out on 10 primigravid women with 49--84 days amenorrhoea undergoing surgical termination of pregnancy. Each woman had two MRI scans of the uterus and cervix. The first scan was performed prior to administration of prostaglandins and the second scan 2.5--3 h following an 800 microg dose of misoprostol given vaginally. Cervical change was assessed by measurement of cervical length, transverse diameter of the cervix, diameter of the internal os and cervical stromal signal intensity. RESULTS: A significant difference in cervical length (P = 0.012), transverse diameter (P = 0.001) and diameter of the internal os (P = 0.008) was detected following the administration of misoprostol. In five women a significant change in one or both components of the cervical stromal signal was detectable and in five women no change could be demonstrated. CONCLUSION: MRI is capable of detecting changes in the physical parameters of the cervix following administration of prostaglandin. However, the changes detected in the stromal signal intensity are less consistent. The potential of MRI as a clinical tool to monitor cervical changes in a variety of clinical situations warrants further investigation.     

Characterization of a highly metastatic, orthotopic lung cancer model in the nude rat

The prevailing subcutaneous nude rodent tumor xenograft models used for biological and preclinical studies do not optimally reflect some important biological properties of cancer, especially invasion and metastasis. Orthotopic models have been developed to address this need. However, for lung cancer none of the available models are optimal, in that none originate from an orthotopic (bronchial) primary site and exhibit extensive extrathoracic metastasis. Our goal was to develop a consistent rodent model of non-small cell lung cancer with both of these properties. Groups of male Rowett nude rats were given 500 rads of gamma radiation and then endobronchially implanted in the right caudal lobe airway with 50 mg of small NCI-H460 tumor fragments taken from an orthotopic donor tumor. They were then sacrificed at selected post-implantation times and evaluated grossly and histologically for animal weight, primary tumor take and size, and metastatic tumor incidence at multiple sites. At a late time point (32–35 days), consistency of primary tumor size and metastasis was estimated by comparing results from four groups of rats implanted on different occasions. The results showed that the primary tumors grew steadily, reaching four grams by days 32–35. Rats gained weight until days 14 to 21, but then began to show cachexia. High metastatic rates (>60%) were seen for mediastinal lymph nodes (by 21 days), and kidney, bone and brain (by 28 days). Mean primary tumor size and the incidences of both regional and systemic metastasis were consistent at 32–35 days in four different groups of six animals. In conclusion, this orthotopic lung cancer model is highly metastatic and consistent in terms of both primary tumor growth and metastatic behavior. It is the only available rodent model of human lung cancer emanating from an endobronchial site and metastasizing to multiple extrapulmonary sites, and should be very useful for both biological and preclinical studies of lung cancer, particularly where studies of antimetastatic activity are of interest, and/or where survival studies are desired.     

A novel spontaneous metastasis model of human osteosarcoma developed using orthotopic transplantation of intact tumor tissue into tibia of nude mice

Evaluation of potential new treatment strategies requires adequate experimental tumor models which resemble the clinical situation as closely as possible. The purpose of the present study was to establish a new human osteosarcoma spontaneous metastasis model using orthotopic transplantation of histologically intact tumor tissue into the tibia of nude mice. Intact tumor pieces, obtained from the 32nd serial passage of subcutaneously growing human osteosarcoma xenografts, were implanted into the proximal tibia in 31 nude mice. Animals were sacrificed and autopsied 2, 4, 6, and 8 weeks after transplantation and examined macroscopically and microscopically for local tumor growth and metastases. All mice developed local intratibial bone tumors that were radiographically and histologically similar to primary human osteosarcoma. Lung metastases were observed in all mice, local and distant lymph node metastases in 15 (48%), and liver metastases in 6 (19%) mice. The microscopic appearance of the metastases was similar to that observed in the donor patientÕs tumor, corresponding subcutaneous xenografts and orthotopically transplanted intratibial tumors. This spontaneous metastasis model of human osteosarcoma in nude mice may resemble a clinical situation and could thus be useful for studies on local tumor growth, metastasis formation and therapy.     

An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential

To provide an investigative tool for the study of osteosarcoma (OSA) biology we have developed a syngeneic (balb/c) murine model of OSA, using cell lines derived from a spontaneously occurring murine OSA (Schmidt et al. Differentiation 1988; 39: 151-60). This model is characterized by orthotopic primary tumor growth, a period of minimal residual disease, spontaneous pulmonary metastasis, and clonally related variants (K7M2 and K12) that differ in pulmonary metastatic potential. Primary tumor and pulmonary metastasis histology was consistent with OSA in human patients. Expression of bone sialoprotein, biglyan, decorrin, and osteopontin was suggestive of bone lineage cells. The development and use of a more aggressive OSA cell line (K7M2) resulted in spontaneous metastasis to the lungs in over 90% of mice, whereas metastases were seen in only 33% of mice when a less aggressive OSA cell line (K12; Schmidt et al. Differentiation 1988; 39: 151-60) was used. Death from metastasis occurred at a median of 76 days using K7M2 whereas no median was achieved after 140 days using K12. Angiogenic potential, characterized by CD31 and factor VIII staining of primary tumors and pulmonary metastases, was greater in the K7M2 model compared to the K12 model. No significant differences in the in vitro or in vivo expression of angiogenesis associated genes (flt1, flt4, TIE1, TIE2, and VEGF) was found between K7M2 and K12. This well characterized and relevant model of OSA will be a valuable resource to improve our understanding of the biology and treatment of metastasis in OSA. This revised version was published online in July 2006 with corrections to the Cover Date.     

A patient-like orthotopic implantation nude mouse model of highly metastatic human ovarian cancer

Clinically relevant animal models of human cancer are important for studies of cancer biology, invasion and metastasis, and for investigating new forms of prognostic diagnosis and therapy. An ovarian tumor line (RMG-1: human clear cell carcinoma of the ovary) previously grown subcutaneously was implanted ortho-topically as intact tissue into the ovarian capsule of 22 nude mice. The tumors showed progressive growth at the orthotopic site in all animals. Tumor-associated serum galactosyltransferase (GAT) tended to be posi-tive in all nude -mice. The tumors invaded or metastasized to the contralateral ovary, retroperitoneum, mesentery and peritoneum, and omentum, and metastasized to the subcutaneous tissue, lymph nodes and distant organs including the liver, kidney, pancreas, and diaphragm. In striking contrast, subcutaneous trans-plantation of this tumor resulted in growth in only 2 of 5 animals with local lymph node and kidney involve-ment but no retroperitoneal or peritoneal involvement. These findings suggest that orthotopic implantation provides a suitable micro-environment in which ovarian cancer can express its intrinsic clinically-relevant properties. This approach is relevant to the clinical features of ovarian cancer and is thought to be a useful model for studies of therapy for this cancer.© Kluwer Academic Publishers 1998     

Isolation of a human gallbladder cancer cell clone with high invasive phenotype in vitro and metastatic potential in orthotopic model and inhibition of its invasiveness by heparanase antisense oligodeoxynucleotides

The mechanisms involved in gallbladder cancer metastasis still remain unclear to date. The poor understanding is due, in part, to the lack of ideal cell line and animal model for study. In the present study, 21 cell clones were isolated from the human gallbladder carcinoma cells GBC-SD and the cell clone GBC-SDH_i with high invasive phenotype was fished out. The invasive phenotype and metastatic potential of GBC-SDH_i were confirmed in a novel surgical orthotopic implantation model of gallbladder cancer in nude mice. Heparanase, an endoglycosidase that degrades heparan sulfate, is a critical mediator of tumor metastasis and angiogenesis. RT-PCR, real time RT-PCR and western blot showed that the expression levels of heparanase were significant difference between GBC-SDH_i and its parent cells. After treated with antisense oligodeoxynucleotides, the heparanase mRNA and protein expression in GBC-SDH_i cells were significantly decreased and its invasive potential in vitro was inhibited in a dose-dependent manner. The study provides a useful cell clone and a clinically relevant orthotopic tumor model for the metastatic study in human gallbladder cancer. The roles of heparanase in gallbladder cancer are also evaluated. This work was supported in part by the Grant from Shandong Science and Technology Committee (No. 003130107 and No. 963000053)     

3.0T MRI 弥散加权成像评价腰椎间盘退变原因的价值

背景：MR弥散加权成像对水分子的扩散运动敏感,能早期了解椎间盘纤维环和髓核的含水量改变,从而明确其退变程度。 目的：通过对109例腰椎间盘的弥散加权成像进行前瞻性研究,旨在提高应用MRI中弥散加权成像序列对椎间盘退变程度和早期变性诊断的认识。 方法：采用Siemens Verio 3.0T 超导磁共振仪。常规平扫包括矢状位T1WI序列及T2WI抑脂序列;弥散加权成像采用SE-EPI序列行矢状位扫描,取b值为800s/ mm2,层厚、间距和显示野同T2WI抑脂序列扫描。根据Pfirrmann等的椎间盘退变分级标准,采用盲法在矢状位T2WI上对符合纳入标准的109例545个腰椎间盘进行分级。将弥散加权成像数据传至工作站,并对表观扩散系数图像进行测量,得到表观扩散系数值。分别画出L1/2-L5/S1椎间盘的感兴趣区,记录数据。 结果与结论：年龄与椎间盘退变分级存在明显相关性,年龄越大高级别数量越多。椎间盘表观扩散系数值影响因素分析：男性与女性各椎间盘表观扩散系数值之间差异无显著性意义(P > 0.05)。L1-S1各椎间盘年龄与表观扩散系数值之间存在负相关(P < 0.05);椎间盘评级与表观扩散系数值之间存在负相关(P < 0.05)。提示通过对表观扩散系数值的研究,弥散加权成像将会成为椎间盘退行性变诊断、特别是椎间盘早期退变、无创评价治疗效果及预后判断的重要技术手段。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程全文链接：     

Magnetic resonance imaging performed on a hydrated mummy of medieval Korea

Previous investigations have shown that magnetic resonance imaging (MRI) can be employed as an efficient non‐invasive diagnostic tool in studies on Egyptian mummies. MRI, moreover, because it produces especially clear images of well‐hydrated tissue, could be a particularly effective diagnostic option for mummies that still retain humidity within tissues or organs. Therefore, in the present study, we tested MRI on a 17th century mummy, one of the most perfectly preserved ‘hydrated mummies’ ever found in Korea, in order to determine the quality of images that could be obtained. We found that the diagnostic value of an MRI scan of the hydrated mummy was not inferior to that of a computed tomography scan. The T1‐ and T2‐weighted magnetic resonance (MR) signals showed unique patterns not easily obtained by computed tomography, the resultant MR images revealing the organ specificities clearly. Overall, the quality of the MR images from the hydrated mummy was superb and the scientific value of MRI in the study of hydrated mummies should not be underestimated.     

Activity of biphenyl matrix metalloproteinase inhibitor BAY 12-9566 in a human breast cancer orthotopic model

Matrix metalloproteinases (MMPs) have been implicated in the invasion, metastasis, and angiogenesis associated with human cancer by mediating the degradation of extracellular matrix components. In this paper, we report data that show that BAY 12-9566, a novel inhibitor of MMPs, inhibits angiogenesis, tumor regrowth, and the growth of lung metastases. BAY 12-9566, at 15–100 μM, inhibited tubule formation by human endothelial cells in an in vitro model, but did not prevent the proliferation of endothelial and human breast cancer cells. In the MDA-MB-435 human mammary carcinoma xenograft model, in which the primary tumor is transplanted into the murine mammary fat pad, BAY 12-9566, administered daily at a dose of 100 mg/kg/day p.o. after resection of the primary tumor, inhibited local tumor regrowth by 58% without causing any toxic effect. In addition, BAY 12-9566 treatment inhibited the number and volume of lung metastases by 57 and 88%, respectively. These effects were highly correlated with the serum concentration of BAY 12-9566 at the end of treatment. The serum of the treated animals, harvested 24 h after the last treatment, and the tumor regrown at the site of tumor transplant in the treated animals, contained less protein with MMP-9 activity (as measured in a gelatin zymography assay) than the corresponding controls. However, no difference in the activity of MMP-2 was observed. Although all clinical trials in cancer involving BAY 12-9566 have been halted, this MMP inhibitor has never been used in clinical trials in breast cancer. These results suggest that the novel MMP inhibitor BAY 12-9566 maybe a useful and safe oral treatment for breast cancer, adjunctive to surgery. This revised version was published online in July 2006 with corrections to the Cover Date.     

高场强MR对孕中期胎儿小脑发育的显示

目的:探讨胎儿小脑结构在不同场强MR图像上的显示情况。方法:48例孕龄在14~22周的胎儿标本,分别进行3.0T与7.0TMR头部扫描,选取不同场强与方位的MR图像,对比分析胎儿小脑结构的显示情况;使用Amira软件测量小脑体积,分析两种场强下获得的体积数值与孕龄的相关关系。结果:3.0T标本MR图像上,T1加权图像对小脑结构显示较T2加权图像清晰,尤其是在20周以后,并随孕龄增大成像分辨率增加。7.0T MR图像对胎脑发育结构的显示以20周前最佳且T2加权图像较T1加权图像效果好,图像质量随孕龄增大分辨率下降。由两种图像重建获得的小脑体积有差异,且其与孕龄的相关关系不同。结论:3.0T T1加权MR图像可以较好显示发育中的胎儿小脑结构;7.0T T2加权MR图像在20周前可以更加清晰显示这些结构。     

核磁共振图像引导的放疗技术进展

利用磁共振成像(MRI)进行图像引导放射治疗(简称:放疗)是近年来受到广泛关注并取得一定研究进展的新技术。该技术结合了MRI成像的优点,具有在线实时追踪肿瘤和临近危及器官以及实时优化放疗计划方案的功能。为了能对该技术的研究有全方位的认识和了解,对国际上在此方面开展的研究进展和动态有所掌握,本文对相关研究进行了综述和概括,以便于让该领域的研究者和医师对此技术的近况有所了解,并展开相应研究。本文就MRI的优点、核磁加速器的研究发展、剂量学相关研究进展和在线引导、自适应优化研究进展等方面进行综述,同时也探讨了这些技术今后可能的发展方向,期望本文综述能为临床医生和相关研究人员了解领域内的研究进展提供一定的参考。     

2型糖尿病患者海马体脑功能连接的磁共振成像研究

目的:应用功能磁共振成像技术研究2 型糖尿病（T2D）患者静息状态下海马功能连接的变化。方法:采集27 例 T2D患者和32例正常人的脑功能磁共振成像信号,选择海马的4个分区作为种子点计算功能连接,对海马与其他脑区的 功能连接强度与临床指标进行相关性分析。结果:与正常人相比,T2D患者的右前海马与梭状回、枕中回之间的功能连接 减弱;左前海马与梭状回功能连接增强;右后海马与距状回功能连接减弱;左后海马与舌回功能连接增强。结论:T2D患 者相关脑区功能连接的改变可能与视觉相关认知功能的损伤有关,这为理解T2D患者海马体的功能提供线索。     

Utility of gradient recalled echo magnetic resonance imaging for the study of myelination in cuprizone mice treated with fingolimod

The availability of high‐field‐strength magnetic resonance imaging (MRI) systems has brought about the development of techniques that aim to map myelination via the exploitation of various contrast mechanisms. Myelin mapping techniques have the potential to provide tools for the diagnosis and treatment of diseases, such as multiple sclerosis. In this study, we evaluated the sensitivity of T₂*, frequency shift and susceptibility measures to myelin levels in a cuprizone mouse model of demyelination. The model was supplemented with two different dosages of fingolimod, a drug known to positively affect demyelination. A decrease in grey–white matter contrast with the cuprizone diet was observed for T₂*, frequency shift and susceptibility measures, together with myelin basic protein antibody findings. These results indicate that T₂*, frequency shift and susceptibility measures have the potential to act as biomarkers for myelination. Susceptibility was found to be the most sensitive measure to changes in grey–white matter contrast. In addition, fingolimod treatment was found to reduce the level of demyelination, with a larger dosage exhibiting a greater reduction in demyelination for the in vivo MRI results. Overall, susceptibility mapping appears to be a more promising tool than T₂* or frequency shift mapping for the early diagnosis and treatment of diseases in which myelination is implicated.