Changes In Microvascular Architecture Research Articles

Microvascular Changes Are Associated with Proteinuria and EMG Changes in Patients with Type 2 Diabetes Using Video Capillaroscopy.

Objectives: Video capillaroscopy is a diagnostic method for evaluating microvascular changes in type 2 diabetes mellitus (T2DM). This study evaluated microvascular changes, including microvascular architecture, capillary distribution (morphology and density), and angiogenesis conditions in T2DM patients via video capillaroscopy. Methods: A total of 256 patients with T2DM enrolled in this study. Based on electromyography (EMG)-nerve conduction velocity results, patients were divided into patients with normal and abnormal EMG. Microalbuminuria was assessed using biochemical urine analysis. Finally, video capillaroscopy was performed to evaluate changes in microvascular architecture, capillary distribution, and angiogenesis status. Results: The differences between microalbuminuria in patients with normal and abnormal EMG were not significant. Other microvascular changes were not significant between normal and abnormal EMG groups. The patients with greater microalbuminuria were at risk of abnormal EMG 2.8 times higher than those with fewer microalbuminuria (odds ratio = 2.804; 1.034-7.601). However, EMG is not a risk factor for microvascular architecture alternation in T2DM (odds ratio = 1.069; 0.323-3.546). Conclusions: Microvascular alternations are common in T2DM and early detection of these changes could help to avoid the progress of nephropathic complications. Also, video capillaroscopy provides a promising diagnostic method for the detection of microvascular alternations in T2DM.

Characterizing the Correlation Between Angiogenesis and Osteogenesis In Vivo Using Multicontrast Functional Imaging in a Calvarial Defect Model

Angiogenesis is a key factor in bone healing that allows the delivery of oxygen, nutrients, inflammatory and bone precursor cells to the defect site. It induces dramatic structural and functional remodeling of the vasculature during the first 4 weeks of bone healing. Although recent advances in optical imaging have elucidated the in vivo relationship between angiogenesis and osteogenesis in a calvarial defect model, these efforts were mostly limited to structural imaging of the vasculature and bone. Therefore, to better characterize changes in vascular function (i.e. blood flow, oxygenation, etc.) during the bone healing cascade we developed a multicontrast optical imaging framework to assess in vivo changes in microvascular architecture using intrinsic optical signal (IOS) imaging; changes in blood flow with laser speckle contrast (LSC) imaging; and bone formation with bright‐field imaging at high spatial (5 µm) and temporal (200 ms) resolutions. With this system we acquired multicontrast images from 10 animals with calvarial defects every 2 days, over 4 weeks (Fig. 1a, d). The bone and vasculature were then digitally segmented from the bright‐field and IOS images for quantitative analysis (Fig. 1b, c). We also euthanized an animal each week for assessing 3D changes in bone volume and vascular architecture using an ex vivo, high‐resolution (10 µm) CT imaging workflow we recently developed called VascuViz (Fig. 2a, b, d). Using this framework, we demonstrated that angiogenic remodeling within the bone defect microenvironment was most robust from post injury day (D) 4 to D10, during which blood vessel length, volume and density all showed significant increase (Fig. 2c). The blood flow exhibited a sudden increase at D6 when angiogenesis started, and the angiogenic vessels were most perfused at D12 (Fig. 1d). These vascular changes peaked by the end of week 2 and plateaued during the next 2 weeks which were correlated with a large increase in bone volume during the first 2 weeks and smaller increase during the last 2 weeks (Fig. 2e). These results indicate that both structural and functional changes of the microvascular system strongly correlate with bone growth during the early stages of bone healing.Next, we plan to include additional indices of vascular function such as vessel maturity and intravascular oxygenation, as well as image‐based hemodynamic models to further characterize the role of the vascular microenvironment during osteogenesis. We believe that this novel imaging framework for characterizing the defect microenvironment can be utilized to inform the design of novel tissue engineering (TE) constructs for craniofacial bone regeneration. Collectively, these advances herald a new era of “image‐based TE”.

Význam flexibilní endoskopie s Narrow Band Imaging pro hodnocení recidivy nádorů hrtanu a hypofaryngu po radioterapii

Background: The dia­gnosis of recurrent upper aerodigestive tumours is difficult, especially in the case of previous curative radiotherapy (RT) or chemoradiotherapy (CRT). Progress in the dia­gnostics of head and neck cancer came with the development of optical endoscopic imaging methods. The aim of this study was to analyse the benefits of flexible Narrow Band Imaging (NBI) in the visualization of suspected recurrence of malignancy in patients after curative RT (CRT). Methods: A total of 58 examined patients in follow-up after curative RT or CRT for laryngeal and hypopharyngeal squamous cell carcinoma were enrolled in the study. All patients underwent transnasal flexible endoscopy in conventional white light and NBI in local anaesthesia. Changes in microvascular architecture (intraepithelial papillary capillary loops – IPCL) have been classified according to Ni. IPCL I–III were considered to be non-suspicious, and therefore no histopathological examination was indicated. IV and V type findings were verified using HDTV NBI intraoperatively with bio­psy sampling and subsequent histopathological correlation was performed. Results: Transnasal videoendoscopic examination with NBI revealed a suspicious finding (IPCL type IV and V) in 23/58 (39.7%) patients, non-suspicious finding (IPCL I–III) in 35/58 (60.3%). Histopathological examination verified the positive finding (precancerous or malignant changes) in 12/23 (52.2%) and negative finding in 11/23 (47.8%) cases. The sensitivity, specificity, positive and negative predictive value of flexible NBI endoscopy were 100%, 76.1%, 52.2% and 100% respectively. According to the Kappa index (K = 0.568), we proved a moderate concordance between flexible NBI endoscopy and histopathological results. Conclusions: Transnasal flexible endoscopy with NBI in outpatient settings contributes to an early detection of pathological changes also in post-radiation altered mucosa of the larynx and hypopharynx, while a correct interpretation of in NBI findings is required to reduce the incidence of false positive results. Keywords: squamous cell carcinoma – Larynx – radiotherapy – narrow band imaging – Ni classification – hypopharynx

Changes in microvascular architecture in colorectal liver metastases

Objective To study the changes in microvascular architecture in colorectal liver metastases so as to provide a theoretical basis for clinical treatment for colorectal liver metastases.Methods 20 fresh cadaveric livers were obtained for this research project.These livers were obtained from deceased patients who had a clinical diagnosis of colorectal liver metastases with detailed clinical imaging data.These patients did not receive any surgical resection or intervention treatment for their liver metastases.After perfusion of the liver with physiological saline,the hepatic artery,portal vein and bile duct were infused with different colors of resin.After successful infusion the livers were corroded to remove the liver tissues,leaving behind the resins.The areas of interest (tumor center and periphery) were located and the changes in microvascular architecture were observed.Results There were 20 specimens from 20 patients with colorectal liver metastases with 64 tumors,23 were more than 3 cm in diameter and 41 less than 3 cm.These tumors were divided into the single nodular,multinodular,and diffuse types.Cancers of more than 3 cm received mainly their blood supply from the hepatic artery.Cancers of less than 3 cm received their blood supply from the portal vein (P =0.004).Scanning electron microscopy showed the microvascular architecture in colorectal liver metastases to be complex and consisted of loops,bifurcated,spiral and networking types.With different tumor diameters,the microvascular diameters showed significant differences (P =0.038,0.012).Conclusions Different sizes of colorectal liver metastases had different sources of the blood supply with different microvascular architectures.These features have significant impact on clinical treatment of colorectal liver metastases. Key words: Liver metastasis ; Microvascular; Colorectal cancer

NBI HDTV Magnifying Endoscopy in Laryngeal Papillomatosis and Laryngeal Spinocellular Cancer

Objective: NBI (Narrow Band Imaging) helps to visualize subtle changes in microvascular architecture linked to neoangiogenesis. Combination of NBI with HDTV (high-definition television) and magnifying endoscopy provides best sensitivity and specificity. The most frequent false positive results were reported in laryngeal papillomatosis where the micro-vascular pattern could be misinterpreted as neoplastic. Method: Patients with clinical diagnosis of papillomatosis or laryngeal cancer were included in the study. NBI HDTV camera head was used in combination with rigid magnifying telescope during microlaryngoscopy. Type and extent of micro-vascular mucosal changes were recorded. Mucosal lesions were removed radically and histologically evaluated and correlated with clinical findings. Results: Preliminary results show that increased neoangiogenesis is present in both laryngeal papillomatosis and laryngeal SCC. The presence of prolonged and enlarged capillary loops was observed in both groups. This yields difficulties in differentiation between both entities. Conclusion: The discrimination of papillomatosis and early stage of laryngeal SCC is difficult even when NBI HDTV magnifying endoscopy is used. Creation of special classification of capillary loop changes in laryngeal mucosa is needed.

Stereological Estimate of the Length of Microvessels and the Number, Proliferation and Apoptosis of Endothelial Cells in Prostate Cancer

Abnormal angiogenesis is a critical feature of many diseases, including cancers and their precursors. Although the association between prostate carcinogenesis and changes in microvascular architecture is well known, these changes are not well-documented from a quantitative point of view. The present work deals with stereological estimates of the number of quiescent and proliferative endothelial cells, and microvessel length in normal and prostate cancer tissues. Un- biased stereological measurements of numerical densities of proliferating cell nuclear antigen immunostained cells, non- proliferating endothelial cells, caspase 3 immunoreactive endothelial cells, and relative length (length density) of mi- crovessels, were performed in control and cancer specimens. There were no changes in either proliferation or apoptosis in carcinoma endothelial cells. A decrease of endothelial cell density, together with an increase of microvessel length den- sity, were detected in prostate cancer specimens. Therefore, the following conclusions can be drawn: a) The increase of angiogenetic activity in prostate carcinogenesis leads to an increment of the microvascular length; b) The amount of endothelial cells per vascular length decreases in prostate cancer; c) There is no decrease of endothelial apoptosis in cancer microvessels. d) The increase of the length den- sity of microvessels in prostate cancer is not directly associated to an enhancement of the endothelial proliferation; and e) The blood supply of epithelium was similar in both cancerous and normal prostate.

Structural Remodeling in the Limb Circulation: Impact of Obesity and Diabetes

Obesity is an emerging epidemic worldwide and threatens cardiovascular health due to the complications of accompanying metabolic dysfunction. One potential mechanism by which these complications are advanced is structural alteration in the microcirculation perfusing target organs. In this brief review, the authors focus on the structural adaptations that occur in the microcirculation, with specific focus on changes in basement membrane thickness and vascular structure. By delineating changes in end-stage disease and recent insights from animal studies, they hope to convince the reader (1) that diabetic disease in the limb is associated with profound changes in arteriolar structure and (2) that parallel changes in microvascular architecture precede the onset of frank type II diabetes.

Agrin in Alzheimer's disease: altered solubility and abnormal distribution within microvasculature and brain parenchyma.

Agrin is a heparan sulfate proteoglycan that is widely expressed in neurons and microvascular basal lamina in the rodent and avian central nervous system. Agrin induces the differentiation of nerve-muscle synapses, but its function in either normal or diseased brains is not known. Alzheimer's disease (AD) is characterized by loss of synapses, changes in microvascular architecture, and formation of neurofibrillary tangles and senile plaques. Here we have asked whether AD causes changes in the distribution and biochemical properties of agrin. Immunostaining of normal, aged human central nervous system revealed that agrin is expressed in neurons in multiple brain areas. Robust agrin immunoreactivity was observed uniformly in the microvascular basal lamina. In AD brains, agrin is highly concentrated in both diffuse and neuritic plaques as well as neurofibrillary tangles; neuronal expression of agrin also was observed. Furthermore, patients with AD had microvascular alterations characterized by thinning and fragmentation of the basal lamina. Detergent extraction and Western blotting showed that virtually all the agrin in normal brain is soluble in 1% SDS. In contrast, a large fraction of the agrin in AD brains is insoluble under these conditions, suggesting that it is tightly associated with beta-amyloid. Together, these data indicate that the agrin abnormalities observed in AD are closely linked to beta-amyloid deposition. These observations suggest that altered agrin expression in the microvasculature and the brain parenchyma contribute to the pathogenesis of AD.

Early endometrial microvascular response during implantation in the rat.

The endometrial microvasculature becomes intimately involved in the events of early implantation. This paper reviews aspects of this microvascular involvement during implantation in the rat. There is a major increase in vascular permeability surrounding the implanting embryo, leading to significant local changes in microvascular architecture. This is followed by a shutdown of the capillaries closest to the embryo as the primary decidual zone develops. At this time, endometrial capillaries adjacent to the primary decidual zone become dilated, with over twice the average diameter of intersite capillaries. Endometrial neutrophils are reduced around the implanting blastocyst, mitigating against a role for these inflammatory mediators in vascular aspects of the implantation process. Angiogenesis does not appear to increase at the implantation site, although there is an increase in production of endometrial endothelial cell migratory signal a few hours prior to the commencement of implantation.

歯肉剥離掻は術後の微細血管構築の形態変化に関する実験的研究 とくに全層歯肉弁剥離創について

本研究の目的は, 全層弁により歯肉を剥離したのち, その治癒過程にかかわる創傷周囲組織の微細血管構築を立体的組織関係を損なうことなく詳細に観察することにある。本実験には, 健康な歯周組織を有する雑種成犬48頭を用い, 上顎左側前歯の一定の位置を実験領域とし, 全層歯肉弁剥離を行った。術後5, 7, 14, 21, 28, 42日の各期間における微細血管鋳型標本をOhtaら (1990) の方法に従って作製し, 走査電顕により観察するとともに, 病理組織学的検索を加え, 比較検討を行った。その結果, 創傷治癒初期過程において, 歯肉骨膜血管網と歯根膜血管網との循環路は, 歯肉骨膜血管網側からよりもむしろ歯根膜血管網側から積極的な回復機序が行われていた。そして, このような循環路の回復過程に起因して, 一時的に歯の支持機能が低下するため, 術後の治癒過程にある組織保護に対して, 慎重な臨床的対応が必要であると考えられる。

Cerebral microvascular architecture following experimental cold injury.

The sequential changes in microvascular architecture following local cold injury in rat brains were studied post mortem by scanning electron microscopy and the vascular casting method. The findings were compared with the results of immunohistochemical studies of injured endothelial cells using the bromodeoxyuridine (BUdR) and anti-BUdR monoclonal antibody technique. Repair of the microvascular architecture had begun by the 3rd day after injury, with hematogenous cells and reactive astrocytes present in the edematous brain participating in the regenerative process. The normal microvascular architecture was reconstructed starting from the edge of the lesion nearest to the brain surface. On the other hand, in the most severely injured part of the brain surface, newly formed microvascular architecture appeared, resembling that of the developing fetal and newborn rat cortex. Seven days after injury, the entire microvascular architecture in the region of the lesion had been reconstructed.

Changes in Brain Microvascular Architecture following Experimental Cold Injury

Sequential changes in the microvascular architecture of rat brains following local freezing injury were studied by scanning electron microscopy involving the cerebrovascular casting method. Repair of the microvascular architecture was initiated on day 3 after injury. Hematogenous cells and reactive astrocytes within the edematous zone participated in the regenerative process. The microvascular architecture was reconstructed from the edge of the lesion toward the brain surface. On the other hand, in small parts of the brain surface subjected to severe, focal freezing, the microvascular architecture was newly formed and resembled that of fetal and newborn rat cortices. Within 7 days after injury, the microvascular architecture was completely repaired.