RGD靶向微泡造影剂的制备及其黏附效能

目的制备一种新型的RGD超声微泡造影剂,探讨其在体外与小鼠血管内皮细胞(b End.3)靶向黏附效果,为肿瘤血管新生超声分子成像奠定基础。材料与方法以"生物素-亲和素"体系制备出RGD靶向微泡造影剂,分为10μg/ml RGD肽封闭组和30μg/ml RGD肽封闭组,未携带RGD肽微泡造影剂作为空白对照。粒径分析仪、普通光镜下进行表征或检测。体外培养小鼠血管内皮细胞,采用多肽封闭静态黏附实验验证靶向性和黏附效率;应用平行板流动腔芯片,设置不同流体剪切力,观察RGD靶向微泡造影剂在血管内皮细胞表面的动态黏附效果。结果测得的RGD靶向微泡粒径为(4.09±0.07)μm。单个细胞表面黏附的微泡个数RGD肽封闭组与RGD-MBs组比较,10μg/ml RGD肽封闭组为(2.98±0.35)个(P<0.05),30μg/ml RGD肽封闭组为(1.78±0.23)个(P<0.001)。10μg/ml和30μg/ml RGD肽封闭实验表明,黏附在单个细胞表面的微泡数量分别降低54.64%和67.00%。在剪切应力1.5 dyne/cm2下,RGD靶向微泡在细胞表面黏附率随着剪切应力增大而增加(P<0.05)。当剪切应力为1.5 dyne/cm2时,RGD靶向微泡在细胞表面黏附率为(48.72±4.26)个,继续增大剪切应力,黏附率降低(P<0.05)。结论 RGD靶向微泡造影剂能特异性地黏附血管内皮细胞,有望作为超声分子探针检测评价整合素ανβ3在肿瘤血管新生中的表达,用于肿瘤的早期诊断及预后检测。     

靶向血管内皮生长因子受体2超声分子成像在小鼠原位胶质瘤血管新生和边界识别中的应用

目的:探讨携带抗血管内皮生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR2)单克隆抗体的超声微泡造影剂(microbubble,MB)在评价小鼠原位胶质瘤血管新生和边界识别中的作用。方法:以生物素-亲和素桥接法构建靶向微泡(MBv),体外鉴定其性质。建立小鼠GL261胶质瘤模型,分别注射MBv和普通微泡(MBc)进行超声造影检查。结果:成功构建偶联抗小鼠VEGFR2单克隆抗体的MBv,造影结果表明MBv较MBc能更好地评价小鼠胶质瘤血管新生和肿瘤边界。结论:MBv是良好的肿瘤靶向造影剂,应用MBv可较好地实现术中评价小鼠胶质瘤血管新生,更好地辅助术中超声导航。     

骨髓基质抗原蛋白2靶向微泡的制备及小鼠肿瘤新生血管超声分子成像研究

目的 研究制备针对骨髓基质抗原蛋白2(BST2)的TMBs造影剂(BST2-TMBs),通过超声分子成像技术对小鼠肿瘤血管内皮细胞进行检测,为肿瘤的发生、发展及早期诊断提供实验依据.方法 将抗BST2的抗体通过生物素-亲和素桥接的方式连接于微泡(MBs)表面,获得BST2-TMBs,在光学显微镜下观察TMBs的形态,用粒径分析仪测定其粒径及其分布;通过体外细胞黏附实验研究TMBs与血管内皮细胞的结合性能,并对小鼠前列腺癌肿瘤血管内皮细胞行超声分子成像,用免疫组织化学染色分析BST2在肿瘤血管内皮细胞的表达.采用SPSS 19.0软件行统计学分析,对独立样本行t检验.结果 制备的BST2-TMBs的平均粒径为1.61μm,其中95％的微泡在1～5 μm之间.BST2 -TMBs能够与血管内皮细胞结合,平均每个视野有(165±25)个TMBs结合在内皮细胞表面,远高于非靶向微泡(IgG-MBs)对照组的(10±3)个微泡(t=10.662,P＜0.01).黏附的TMBs能够明显增强内皮细胞的超声信号强度,TMBs为27.93±5.14(灰度值),非靶向微泡为3.61±1.67(灰度值)(t=7.239,P＜0.01).小鼠在体肿瘤超声分子成像表明:BST2-TMBs处理组在微泡注射7min时信号强度(扣除微泡击碎后的信号强度)为38.79±0.29(灰度值),能保持47.65％的微泡注射30 s时的信号强度(灰度值81.40±0.37),而IgG-MBs处理组在微泡注射7 min时的信号强度(扣除微泡击碎后的信号强度)是9.46 ±0.17(灰度值),仅能保持11.39％的微泡注射30 s时的信号强度(灰度值83.01±0.60).相比之下,TMBs在肿瘤部位的超声信号强度较非靶向微泡提高4.27倍(t=65.587,P＜0.01).免疫组织化学证实BST2蛋白在小鼠前列腺癌肿瘤血管内皮细胞上有表达.结论BST2 -TMBs可以用于小鼠前列腺癌血管内皮细胞的超声分子成像,这为肿瘤的发生发展以及早期诊断提供了实验依据.     

放疗对结肠癌细胞种植瘤血管生成的影响

目的:观察荷瘤鼠接受放疗前后,肿瘤组织内微血管密度及血管内皮生长因子表达的变化,探讨放疗对肿瘤血管生成的作用.方法:20只小鼠接种结肠癌细胞SW480,随机分为对照组和放疗组.放疗组接受总量20 Gy的照射.放疗结束后第5 d处死小鼠,免疫组化法测定肿瘤组织内微血管密度和肿瘤细胞VEGF表达阳性率,比较两组间的差异.结果:放疗组和对照组肿瘤组织内MVD值分别为8.40±4.22和14.40±4.65 (P=0.007);VEGF表达阳性率分别为2.07±0.569和1.44±0.608(P=0.028),均有明显差异.结论:放疗可减少荷瘤鼠肿瘤的血管数量,提高血管内皮生成因子的表达.     

靶向超声分子成像评价血管新生的研究进展

靶向超声分子成像技术是指将带有特定配体的靶向超声微泡经静脉注入体内,通过配体与受体结合的方式,使超声微泡选择性地聚集于靶组织或靶器官,并通过对比超声检查产生靶组织细胞水平、分子水平显影的一种新兴的成像技术。该技术标志着超声影像学从非特异性的物理成像向特异性的靶向分子成像的转变,是当今世界研究的热点之一,本文就应用靶向超声分子成像评价血管新生的相关进展作一简述和探讨。     

188Re-奥曲肽在荷瘤裸鼠体内分布的实验研究

目的研究188Re-奥曲肽在荷瘤裸鼠体内的分布,为进一步肿瘤靶向治疗奠定基础.方法16只荷人H460非小细胞肺癌的BALB/c裸鼠分为4组,经尾静脉注射188Re-奥曲肽18.5MBq(0.2ml),于注射后2h,4h,24h,48h每个时间点处死一组裸鼠,取血液、肿瘤组织及主要脏器测量其放射性计数率值,经放射性衰变校正后计算每克组织的百分注射剂量率(%ID/g),观察标记物在动物体内的生物学分布.另2只荷瘤裸鼠同样尾静脉注射相同剂量的188Re-奥曲肽,于注射后相同时间点行SPECT扫描,利用感兴趣区技术对肿瘤/非瘤组织放射性比值(T/NT)进行半定量分析.结果188Re-奥曲肽标记率达(95.3±1.8)%,188Re-奥曲肽在荷瘤裸鼠体内主要分布于肿瘤组织、肝脏、肾脏及肠道,肿瘤部位在4h摄取达到高峰9.8%ID/g,此时SPECT在肿瘤部位有明显的放射性核素浓聚,T/NT在尾静脉药物注射后24h达到高值为7.1.结论188Re-奥曲肽在BALB/c荷瘤裸鼠体内对人非小细胞肺癌具有靶向定位作用,其在肿瘤部位的分布具有较高的T/NT,188Re-奥曲肽有望用于表达生长抑素受体肿瘤的核素靶向治疗.     

携带抗白细胞介素-2受体α单抗靶向超声微泡和对比超声结合评价肾缺血-再灌注损伤

目的探讨携带抗白细胞介素-2受体α(IL-2Rα)单抗靶向超声微泡和对比超声结合评价肾缺血再灌注损伤(IRI)的可行性。材料与方法采用"亲和素-生物素"桥接法构建携抗IL-2Rα靶向超声微泡(MBIL-2Rα)和携同型抗体对照微泡(MB)。10只左肾缺血50min的小鼠,再灌注24h后,随机先后注入MBIL-2Rα和MB(间隔30min),分别于注入5min后行对比超声检查,并测量肾的声强度(VI)。结果对比超声图像显示MBIL-2Rα组左肾造影显著增强,VI值高达21.6±4.8U,而在MB组左肾仅见轻度造影增强,VI值为9.7±2.9U,两组间差异有统计学意义(P<0.05)。但无论是MBIL-2Rα组还是MB组左肾VI值均明显高于右侧肾脏VI值(3.8±1.5U,3.7±1.7U,P<0.05)。两组右侧肾脏之间VI值未见明显差异。结论 MBIL-2Rα和对比超声相结合能够有效评价肾IRI,从而对肾移植后的排斥反应提供有价值的信息。     

靶向微泡成像显示肿瘤新生血管:微型PET动态扫描评估小鼠体内的生物学分布

目的通过微型PET对活体小鼠的动态扫描来评价肿瘤血管内皮生成因子受体2(VEGFR2)相关的微泡靶向肿瘤新生血管在小鼠体内的分布。材料与方法 本     

心脏肾上腺素能神经的PET应用

目的研究188Re-奥曲肽在荷瘤裸鼠体内的分布,为进一步肿瘤靶向治疗奠定基础。方法16只荷人H460非小细胞肺癌的BALB／c裸鼠分为4组,经尾静脉注射188Re-奥曲肽 18．5MBq(O．2ml)．于注射后2h,4h,24h,48h每个时间点处死一组裸鼠,取血液、肿瘤组织及主要脏器测量其放射性计数率值,经放射性衰变校正后计算每克组织的百分注射剂量率(％ID／g),观察标记物在动物体内的生物学分布。另2只荷瘤裸鼠同样尾静脉注射相同剂量的188Re-奥曲肽,于注射后相同时间点行SPECT扫描,利用感兴趣区技术对肿瘤／非瘤组织放射性比值(T／NT)进行半定量分析。结果188Re-奥曲肽标记率达(95．3±1．8)％,188Re-奥曲肽在荷瘤裸鼠体内主要分布于肿瘤组织、肝脏、肾脏及肠道,肿瘤部位在4h摄取达到高峰9．8％ID/g,此时SPECT在肿瘤部位有明显的放射性核素浓聚,T／NT在尾静脉药物注射后24h达到高值为7．1。结论 188Re-奥曲肽在BALB／c荷瘤裸鼠体内对人非小细胞肺癌具有靶向定位作用,其在肿瘤部位的分布具有较高的T／NT,188Re．奥曲肽有望用于表达生长抑素受体肿瘤的核素靶向治疗。     

99Tcm标记反义肽核酸探针的制备及其荷瘤裸鼠体内分布

目的 探讨99Tcm标记反义肽核酸(PNA)探针的新方法及其在生物体内的分布.方法 合成12mer且5'端含有四肽G-(D)-A-G-G的c-myc mRNA反义、无义PNA片段,利用G-(D)-A-G-G形成的N4结构为螯合基团进行99Tcm标记,用聚酰胺薄膜层析法和高效液相色谱仪法(HPLC)测定其标记率和标记物的稳定性,并行人结肠癌荷瘤裸鼠体内分布[每克组织百分注射剂量率(%ID/g)]及显像研究.采用SAS 6.22软件对数据进行分析.结果 反义、无义PNA片段合成物的纯度>95%.99Tcm标记c-myc mRNA反义、无义PNA的标记率>95%,标记物室温放置18 h测定其标记率仍可达95%以上.c-myc mRNA反义、无义PNA片段4～8℃下放置3个月标记率仍>95%.HPLC测定标记物呈单峰.99Tcm标记c-myc mRNA反义PNA主要分布在荷瘤鼠肾、脾、肿瘤、肠道、肝组织中,99Tcm标记c-myc mRNA无义PNA在荷瘤鼠血液、脾、肾、肝及肺组织中分布较多;注射后4 h两者在荷瘤鼠肿瘤组织中的分布差异有统计学意义[(1.11±0.12)%ID/g和(0.14±0.02)%ID/g;t=14.75,P<0.01].99Tcm标记c-mycmRNA反义PNA在小鼠体内肿瘤/肌肉、肿瘤/肺的摄取比值较高,肿瘤显像明显.结论 用99Tcm标记c-myc mRNA反义、无义PNA的方法简单,标记率高,标记物稳定,前者有望成为一种新型肿瘤显像剂.     

Stress MR imaging for evaluation of popliteal artery entrapment

The popliteal artery entrapment (PAE) syndrome has been recognized as a cause of arterial occlusion in young people. It is the result of an anomaly of the relationship between the popliteal artery and the gastrocnemius muscle. Eight young healthy volunteers (16 legs) and six patients (10 legs) with suspected PAE underwent magnetic resonance (MR) imaging. Gradient-echo images were obtained in axial planes with the leg at rest and during active plantar flexion against resistance. Imaging at rest allowed identification of PAE signs in only one leg, which had an anomalous medial course of the popliteal artery. In the other cases, only the stress technique was able to show signal loss in the popliteal artery due to muscular compression (two legs) or the presence of accessory muscle slip around the vessel (two legs), as confirmed at surgery. MR imaging is therefore a useful technique for the diagnosis of PAE because of its capability of combining information obtainable with other modalities.     

MR imaging of muscle and tender points in fibromyalgia

Fibromyalgia is a syndrome manifested by chronic, diffuse muscu-loskeletal aching and soreness, palpable muscle tender points, and other symptoms. Standardized clinical diagnostic criteria have recently been developed. Skeletal muscle has been postulated as the end organ in this disease. Biochemical, histologic, electromyographic, and conventional radiographic studies have demonstrated no definitive abnormality. This study sought to establish whether magnetic resonance (MR) imaging could demonstrate any abnormality in these patients. Eighteen patients were entered in the study, 14 of whom were able to complete their examinations. T1 -weighted, T2-weighted, gradient-echo, and STIR (short-tau inversion-recovery) sequences were performed in all patients, with selected patients examined with T1weighted, gadopentetate dimeglu-mine-enhanced sequences. The trapezius and suboccipital regions were imaged in patients who, clinically, had active fibro-myalgia. No abnormalities could be detected. The authors conclude that the conventional MR imaging used in this study was unable to depict any primary skeletal muscle abnormality in fibromyalgia.     

Uterine contractions: Possible diagnostic pitfall at MR imaging

A total of 206 nongravid patients with various gynecologic problems underwent pelvic magnetic resonance (MR) examinations that included both sagittal T2-weighted and contrast agent–enhanced T1-weighted images. MR images were retrospectively reviewed to identify changes in endometrial configuration on serial images obtained during the same MR examination. In 20 MR examinations (all in women of reproductive age), endometrial distortion due to myometrial bulging was noted on T2-weighted or contrast-enhanced T1-weighted images. It was absent on other MR images obtained at different times. Myometrial bulging exhibited low signal intensity in 18 examinations. The finding resembled adenomyosis or leiomyoma on T2-weighted or contrast-enhanced T1-weighted images. These results evidence the presence of transient myometrial bulging and transient low-intensity myometrium in the nongravid uterus. This phenomenon is thought to represent uterine contraction. Clinicians should be aware of the potential presence of transient low-signal-intensity myometrial bulging that could present diagnostic problems in the normal uterus.     

Controversies in cervical spine imaging in trauma patients

No area of emergency radiology has generated as much discussion in recent years as the subject of cervical spine imaging for trauma patients. This review will be in three parts. The first will examine the indications for cervical imaging and will focus on those factors that make patients at high risk or low risk for cervical injury. The second part will discuss the merits of radiography and computed tomography as the main screening diagnostic examination. In addition to the roles of each modality in the evaluation process, such factors as efficacy of diagnosis, time (duration) of study, and cost will be discussed. Finally, the third part will explore the methods currently employed to clear the cervical spine in comatose patients.Presented at the Annual Meeting of the American Society of Emergency Radiology, Las Vegas, Nevada, 22–25 October, 2003     

Brodie Abscess: MR imaging appearance in 10 patients

The magnetic resonance (MR) imaging features of Brodie abscess have not yet been fully evaluated. Ten patients with Brodie abscess, eight of long bone and two of vertebra, were studied with MR imaging. Long bone abscess had a characteristic “target” appearance with four layers: (a) a center with low signal intensity on T1-weighted images and high signal intensity on T2-weighted and STIR (short-inversion-time inversion recovery) images, (b) an inner ring isointense to muscle on T1-weighted images and with high signal intensity on T2-weighted and STIR images, (c) an outer ring hypoin-tense on all images, and (d) a peripheral halo hypointense on T1-weighted images. In six of eight cases, a soft-tissue mass was found. The two vertebral abscesses had a less specific appearance, with low signal intensity on T1-weighted images and high signal intensity on T2-weighted and STIR images. Only the peripheral halo was clearly identified in both cases.     

Dynamic contrast-enhanced MR imaging assessment of vascularized free fibular grafts

Magnetic resonance (MR) imaging may be a noninvasive method for assessing perfusion of vascularized bone grafts placed for treatment of avascular necrosis. One proximal femur of seven beagles was devascularized, with insertion of a vascularized fibular graft. MR imaging at 1 week (seven dogs) and 6 weeks (five dogs) after surgery included pre- and postcontrast spin-echo sequences, unenhanced twodimensional time-of-flight (TOF) vascular imaging, and dynamic gradient-echo imaging during infusion of gadolinium. Relative signal intensity values of selected regions obtained from the dynamic gradientecho images were plotted as percent enhancement versus time. In the operated hip, MR imaging did not show enhancement in six of seven femoral heads and greater trochanters at 1 week after surgery, with similar results after 6 weeks. MR imaging of fibular grafts 6 weeks after surgery showed an initial rapid increase in enhancement and a subsequent slower increase in five of five dogs, although no enhancement was seen in six of seven dogs at 1 week. These findings contrasted with a rapid initial increase in enhancement followed by slow decline in non-operated hips. Two-dimensional TOP imaging did not show the vascular pedicle of the graft in any dog. Findings of radionuclide bone scanning performed 1 week after surgery were consistent with devascularization of the operated femur and fibular graft. However, tetracycline distribution and histologic findings confirmed the viability of five of five grafts within the devascularized femurs 6 weeks after surgery. Thus, dynamic contrast-enhanced MR imaging at 6 weeks after surgery is valuable for assessing vascular bone graft perfusion, while similar imaging at 1 week may suggest otherwise.     

Right-side aortic arch with aneurysm of aberrant left subclavian artery: MR imaging appearance.

Reports of aneurysms of the subclavian artery in both normal and anomalous aortic arches have been rare. The authors describe a patient with a right-side aortic arch and an aneurysm of the aberrant left subclavian artery, which, to the authors' knowledge, is a previously unreported association. At presentation, the aneurysm appeared as a calcified left superior mediastinal mass. Magnetic resonance imaging enabled preoperative diagnosis and guided surgical planning.     

Adrenal tissue characterization with 0.5-T MR imaging: Value of T2*-weighted images

The authors investigated the value of magnetic resonance (MR) imaging at 0.5 T for distinguishing adrenal adenomas from adrenal metastases. The series included 23 adrenal adenomas (18 nonhyperfunctioning, five hyperfunctioning) and 23 adrenal metastases from various organs. Adrenal tumor–liver signal intensity ratios on T1-, T2-, and T2*-weighted images were calculated for adrenal tissue characterization. Adrenal adenomas were more precisely distinguished from adrenal metastases on T2*-weighted images (21 of 23, 91%) than on T2-weighted images (15 of 23, 65%). T1-weighted images were not useful for this distinction. In conclusion, T2*-weighted images were better than routine T2-weighted images for distinguishing adrenal adenomas from adrenal metastases. It can be postulated that the total signal intensity of adrenal adenomas, which contain some fat components, decreased on T2*-weighted images because of an out-of-phase effect.     

MR angiography of congenital heart disease: Value of segmented two-dimensional inflow technique and maximum-intensity-projection display

Magnetic resonance (MR) angiography of the cardiovascular system was evaluated in 41 patients with congenital heart disease by using a two-dimensional (2D) inflow technique based on a magnetization-prepared gradient-echo pulse sequence with segmented k-space data acquisition and electrocardiographic gating at 0.5 T. Inversion and saturation prepulses were used to suppress stationary tissue and enhance intravascular signal. Presaturation slabs were applied where certain vascular structures had to be suppressed. Sequence parameters were optimized by evaluating signal intensity and contrast characteristics for various flip angles and inversion and saturation delay times. The heart and intrathoracic vasculature were encompassed with 40–50 overlapping sections. Both 2D angiograms and maximum-intensity-projection images were evaluated. Combining data sets acquired in the sagittal and transverse orientations provided the most satisfactory information about the pulmonary arteries. The highest signal-to-noise ratios were obtained with a flip angle of 65° and short prepulse delay times. Two-dimensional MR angiography can provide useful diagnostic information but requires a thorough understanding of in-plane and hemodynamically induced signal intensity changes.