Imaging of insulin factory: Is it just imagination or approaching reality?
Imaging of insulin factory: Is it just imagination or approaching reality?
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DOI：
10.1111/j.2040-1124.2012.00236.x
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发表时间：
2012-10-18
影响因子：
3.2
通讯作者：
Yagihashi S
中科院分区：
文献类型：
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作者：
Yagihashi S
临床分期的确定和疾病的严重程度对于管理和预测患者的预后是至关重要的。胰岛素分泌量和b细胞质量都被认为是1型或2型糖尿病严重程度和分期的指标。免疫过程对b细胞的快速破坏是1型糖尿病的关键发病过程。1型糖尿病患者发病时，几乎所有的胰腺b细胞都被破坏了。最近，同样在2型糖尿病中，b细胞团缓慢但进行性下降通常伴随淀粉样蛋白沉积被发现是一个病理标志。因此，当做出诊断时，我们必须决定患者处于哪一阶段的糖尿病。为此，我们需要知道特定糖尿病患者的胰岛受损程度，以确定最佳治疗选择。我们也很想知道这种治疗是否可以阻止b细胞的破坏，或者它是否促进了它们的复制。此外，在1型糖尿病患者中，尽管胰岛移植是最终选择的治疗方式，但跟踪移植细胞的存活情况以了解胰岛移植是否成功是至关重要的。因此，糖尿病患者b细胞质量的量化似乎是一个主要的研究课题，研究人员努力探索血液生物标志物来预测b细胞质量的近似值；还探索了空腹高血糖、糖化血红蛋白浓度、C肽、胰岛素生成指数或b细胞功能的稳态模型评估(HOMA-b)。然而，这些指数被发现是不完整的，因为它反映了实际的b细胞质量。或者，最终目标可能是通过身体成像直接显示b细胞。胰岛成像的主要问题是体积太小。100g左右的胰腺(仅占胰腺的1~2%)，其总体积可达1~2g(Cc)。每个胰岛的大小(50~500lm)也太小了。我们经常会遇到许多只由几个内分泌细胞组成的小岛。此外，它们广泛分布于整个胰腺，与周围组织的对比度较低。由不同细胞组成的胰岛图像不均匀，与胰腺外分泌信号的区别不大，难以识别组织的特异性。这样的解剖特征不可避免地需要与背景实质形成对比的胰岛图像的增强。尽管使用激光扫描显微镜的光学方法在动物模型中显示活的b细胞具有一定的前景，但由于其侵袭性和对LIGHT1的有限组织穿透性，将其应用于人类是不可行的。对于胰岛三维结构的检测，由于其无创性，将其应用于正电子发射断层扫描(PET)或磁共振成像(MRI)更具现实意义。在过去的十年里，高分辨率的PET和MRI扫描仪已经被开发出来，糖尿病患者的胰腺的背景病理也已经被建立。由于临床影像方法的高度敏感性，PET扫描被初步应用于人体，但结果令人失望。由于正电子发射计算机断层扫描的空间分辨率有限，磁共振成像被认为更适合于位于人体深部的天然胰岛的成像。1.动物体内移植胰岛的磁共振成像显示了良好的图像，为检测天然…提供了期望
The determination of clinical staging and the severity of disease are essential to the management and prediction of the prognosis of a patient. Insulin secretory capacity and b-cell mass are both considered to be indicators of severity and staging of either in type 1 or type 2 diabetes. Rapid destruction of b-cells by immune processes is a key pathogenetic process in type 1 diabetes. At onset of the disease, nearly all pancreatic b-cells are destroyed in type 1 diabetes. More recently, also in type2 diabetes, slow but progressive decline of b-cell mass often accompanied by amyloid deposition was found to be a pathological hallmark. Thus, we have to make a decision about which stage of diabetes the patient stands in when the diagnosis is made. To this end, we need to know to what extent the islets are damaged in a given diabetic patient to determine the best choice of treatment. We are also curious to know whether the treatment can stop the destruction of b-cells or if it promotes their replication. Furthermore, in type 1 diabetic patients, although islet transplantation is a final choice of treatment modalities, it is crucial to follow the survival of the implanted cells to know whether islet transplantation has been successful or not. As such, quantitation of b-cell mass in diabetic patients seems to be a prime subject of research and investigators have made efforts to explore the blood biomarkers to predict the approximate value of b-cell mass; fasting hyperglycemia, glycated hemoglobin concentrations, C-peptide, insulinogenic index or homeostasis model assessment of b-cell function (HOMA-b) have been explored as well. These indices are found to be incomplete, however, for the reflection of actual b-cell mass. Alternatively, the ultimate goal might be direct visualization of b-cells by body imaging. The major problem of the imaging of the islet is that its volume is too small. The total volume might reach only 1~ 2 g (cc) in approximately 100g pancreas (only 1–2% of the pancreas). The size of each islet (50~ 500 lm) to make an image is also too small. We frequently encounter numerous small islets composed of just a few endocrine cells. In addition, they distribute widely in the whole pancreas with low contrast difference from the surrounding tissues. The islet composed of heterogeneous cells yields an inhomogeneous image, not much is discriminated from the intensities of the exocrine pancreas, which makes it difficult to identify the specificity of the tissues. Such anatomical characteristics inevitably require augmentation of the islet image in contrast to background parenchyma. Although optical methods using laser scanning microscopy showed some promise for the visualization of live b-cells in animal models, it was not feasible to apply to humans because of its invasiveness and limited tissue penetration of light1. For the detection of 3-D architecture of islets, application of the imaging to positron emission tomography (PET) scans or magnetic resonance imaging (MRI) is more realistic because of non-invasiveness. High-resolution PET and MRI scanners have been developed in the past decade, and the background pathology of the pancreas in diabetic patients has also been established. Because of the high sensitivity of clinical imaging modalities, PET scan was preliminarily applied to humans, but the results were disappointing. As the spatial resolution of PET scan is fairly limited, application of MRI is proposed to be more suitable for the imaging of native islets of the pancreas located in deep positions of the body 1.Introduction of MRI imaging of the transplanted islets in vivo in animals showed promising images, providing us with an expectation for the detection of native …
影响因子：
8.2
作者：
Andralojc, K.;Srinivas, M.;Brom, M.;Joosten, L.;de Vries, I. J. M.;Eizirik, D. L.;Boerman, O. C.;Meda, P.;Gotthardt, M.
通讯作者：
Gotthardt, M.
影响因子：
5.8
作者：
Schneider, S.
通讯作者：
Schneider, S.
影响因子：
7.7
作者：
Lamprianou, Smaragda;Immonen, Riikka;Meda, Paolo
通讯作者：
Meda, Paolo