Characterisation of tumour vasculature in mouse brain by USPIO contrast-enhanced MRI

To enhance the success rate of antiangiogenic therapies in the clinic, it is crucial to identify parameters for tumour angiogenesis that can predict response to these therapies. In brain tumours, one such parameter is vascular leakage, which is a response to tumour-derived vascular endothelial growth factor-A and can be measured by Gadolinium-DTPA (Gd-DTPA)-enhanced magnetic resonance imaging (MRI). However, as vascular permeability and angiogenesis are not strictly coupled, tumour blood volume may be another potentially important parameter. In this study, contrast-enhanced MR imaging was performed in three orthotopic mouse models for human brain tumours (angiogenic melanoma metastases and E34 and U87 human glioma xenografts) using both Gd-DTPA to detect vascular leakage and ultrasmall iron oxide particles (USPIO) to measure blood volume. Pixel-by-pixel maps of the enhancement in the transverse relaxation rates (Delta R(2) and Delta R(2)(*)) after injection of USPIO provided an index proportional to the blood volume of the microvasculature and macrovasculature, respectively, for each tumour. The melanoma metastases were characterised by a blood volume and vessel leakage higher than both glioma xenografts. The U87 glioblastoma xenografts displayed higher permeability and blood volume in the rim than in the core. The E34 glioma xenografts were characterised by a relatively high blood volume, accompanied by only a moderate blood-brain barrier disruption. Delineation of the tumour was best assessed on post-USPIO gradient-echo images. These findings suggest that contrast-enhanced MR imaging using USPIOs and, in particular, Delta R(2) and Delta R(2)(*) quantitation, provides important additional information about tumour vasculature.     

SPIO与Gd-DTPA增强对裸鼠肾癌移植瘤显影价值对照研究

目的:比较SPIO与Gd-DTPA增强对裸鼠肾癌移植瘤显影价值.方法:种植人肾癌Ketr-3细胞的雄性裸鼠14只,随机分为2组:SPIO组7只,Gd-DTPA组7只.SPIO组先行T_2 WI平扫,后快速注入Reso-vist,注药后即时、10min重复T_2WI序列.Gd-DTPA组先行T_1WI平扫,后快速注入Gd-DTPA,注药后即时、10rain重复T_1WI序列.扫描结束分别测量两组移植瘤增强前后的信号强度及计算相对增强率.结果:SPIO组注入Resovist后,即时移植瘤T_2信号强度(SI)开始下降,10min后T_2SI逐渐回复.Gd-DTPA组注入Gd-DTPA后,即时移植瘤T_1SI明显增加,10min后T_1SI亦维持于较高水平.结论:Gd-DTPA对于肾癌移植瘤的诊断有着较长的强化时间窗,且强化效果较SPIO更明显.     

听神经瘤的MRI诊断

目的:探讨MRI对本病的诊断价值。方法:22例经手术病理证实资料完整的听神经瘤。结果:22例中有2例微小听神经瘤,MRI表现病侧第Ⅶ、Ⅷ神经束局部结节状等或稍低信号。注射Gd-DTPA后瘤体呈小结节状均匀强化。20例为大的听神经瘤,T1WI呈低或稍低、低混杂信号,T2WI呈高信号或稍高、高混杂信号,患侧第Ⅶ、Ⅷ神经束比对侧增粗,与肿瘤无明确分界,两者信号变化一致,注射Gd-DTPA后肿瘤呈明显不均匀性、均匀性或环状强化。本组定位,定性诊断准确率为100%。结论:MRI是诊断听神经瘤非常有效的方法,应作为听神经瘤的术前首要检查方法。     

Magnetic resonance imaging of osteosarcoma using a bis(alendronate)-based bone-targeted contrast agent

Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd₂-diethylenetriaminepentaacetate-bis(alendronate) (Gd₂-DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pK_a, complex constant, and T₁ relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd₂-DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd₂-DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r₁) of 7.613 mM⁻¹ s⁻¹ (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd₂-DTPA-BA was much higher than that of Gd-DTPA after intravenous injection to the mice. More importantly, the MR imaging of osteosarcoma was significantly improved by Gd₂-DTPA-BA. The signal intensity of Gd₂-DTPA-BA reached 120.3% at 50 min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd₂-DTPA-BA in the osteosarcoma-bearing mice was very high to 130 at 180 min. Furthermore, the contrast enhancement could also be found in the lung due to metastasis of osteosarcoma. Gd₂-DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases.     

Degenerative disk vascularization on MRI: correlation with clinical and histopathologic findings

 Objective. This prospective study was designed to determine the MRI features, clinical significance, and correlation to histopathologic findings of secondary vascularized degenerative intervertebral disks. Materials and methods. Fifty-three patients with localized painful spine syndrome were investigated prospectively by contrast-enhanced MRI. Pain was not predominantly radiating and there was no clinical evidence of spinal infection. In all patients sagittal SE T1-weighted, fast-SE T2-weighted or turbo-STIR, and T1-weighted frequency-selective fat-suppressed images were obtained. Results. We identified 37 vascularized disks in 26 patients. In 18 patients the changes had occurred spontaneously, in 6, the affected disk had been operated on previously, and 2 patients had spondylolisthesis. In 15 patients, vascularization was accompanied by medullary edema adjacent to the vertebral endplates. In one of the vascularized disks, herniation was also found. In seven patients, ventral diskectomy was performed. Histopathologic findings confirmed disk vascularization in six of seven cases. Conclusions. Degenerative, band-like disk vascularization is a feature which is associated with local pain. It is demonstrated by contrast-enhanced MRI. Degenerative disk vascularization is an important differential diagnosis to bacterial spondylodiskitis. It can be a cause of pain in patients with postdiskectomy syndrome.     

Standard dose Gd-DTPA dynamic MR of renal arteries

Renal MR contrast enhancement depends on the timing of image acquisition. Limited human trials have demonstrated efficacy of renal artery stents on salvage of renal function. This study assessed the ability of dynamic gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) administration to demonstrate renal artery stenosis and renal stent patency compared to conventional angiography as the gold standard. Twenty subjects referred for renal angiography underwent 22 dynamic MR studies, including 7 with renal artery stenting (Palmaz P204 or P201, Johnson & Johnson, Sydney, Australia). All were examined with conventional angiography and after dynamic Gd-DTPA infusion. Coronal MR images of the kidneys were acquired using a GE Signa 1.5-T magnet (General Electric Medical Systems, Milwaukee, WI) (fast spoiled gradient echo [FSPGR]; TE = 4.2 msec, TR = 68–150 msec, flip angle = 75°) 0 to 600 seconds after iv bolus injection of 15 ml of Gd-DTPA during sequential breath-hold acquisitions, 13 to 32 seconds each. All 51 renal arteries (13 stenosed, 38 normal) were detected with dynamic MRI. Severity of renal artery stenosis was classified correctly with an accuracy of 98% (95% confidence interval [CI]: 85–100), yielding 98% specificity and 100% sensitivity. All nine renal stents were visualized with 100% accurate patency documentation. FSPGR MRI with bolus Gd-DTPA administration can provide adequate time and spatial resolution to demonstrate renal artery stenosis.     

Contrast-enhanced,k-space-centered,breath-hold MR angiography of the renal arteries and the abdominal aorta

The purpose of this study was to evaluate the capability of contrast-enhanced breath-hold fast imaging with steady-state precession (FISP) three-dimensional MR angiography (MRA) to detect stenotic lesions of the abdominal aorta, the renal arteries, and the iliac arteries by using a k-space-centered 20-ml gadolinium-diethylene pentaacetic acid (Gd-DTPA) bolus. Fifty patients were studied before conventional x-ray angiography. Contrast-enhanced breath-hold FISP three-dimensional MRA was applied in the coronal view, centered at the renal arteries. Twenty ml of Gd-DTPA was used in all subjects. A test bolus was applied to determine the injection time for the k-space-centered bolus injection. Of 300 segments, 284 segments were classified correctly, 11 were overestimated, and five were underestimated. Sensitivity was 98%, specificity was 96%, positive predictive value was 96%, negative predictive value was 98%, and accuracy was 97%. Of the 50 patients studied, 43 were staged correctly. No venous overlay was seen in 31 patients; partial overlay was seen in 16 patients, and venous structure overlay obscuring arterial anatomy was found in two patients. Six of nine accessory renal arteries could be identified by MRA. Intraobserver variability was .94. This study has shown the ability of contrast-enhanced breath-hold FISP three-dimensional MRA to detect and grade vascular lesions in the abdominal aorta and the renal arteries. The method may serve as a screening tool in the future.     

Multi-parameter MRI to investigate vasculature modulation and photo-thermal ablation combination therapy against cancer

Nanotransducer-mediated photothermal therapy (PTT) has emerged as an attractive therapy modality against cancer, but its efficacy is often limited by the amount of nanoparticles delivered to tumors. Previous studies showed a vasculature modulation treatment, which dilates or prunes tumor blood vessels, may enhance tumor uptake of nanoparticles. However, exploiting these approaches for improved PTT has seldom been studied. In this study, we investigated the impact of mild hyperthermia or anti-angiogenesis therapy on PTT. Briefly, we gave tumor-bearing balb/c mice low doses of sunitinib or submerged tumors in a 42?°C water bath. Next, we injected PEGylated reduced graphene oxide (RGO-PEG) and irradiated the tumors to induce PTT. We then followed up the treatment with multi-parameter MRI. Contrary to expectation, both vessel modulation strategies led to diminished PTT efficacy. Our results show that vessel modulation does not warrant improved PTT, and should be carefully gauged when used in combination with PTT.     

Gd-DTPA 增强 MRI 胸部组织序列信号变化的临床研究

目的：通过对肺癌和正常胸部组织的Ｇｄ－ＤＴＰＡ增强前后的信号强度、信噪比和相对信噪比的分析，探讨增强ＭＲ在胸部的应用价值。方法：用ＤＩＡＳＯＮＩＣ０．３５Ｔｅｓｌａ超导型ＭＲ成像仪。先常规平扫Ｔ１ＷＩ、Ｔ２ＷＩ，然后按０．１ｍｍｏｌ／ｋｇ体重，静脉内一次性注入Ｇｄ－ＤＴＰＡ（维影钆胺注射液）。立即行兴趣部位Ｔ１ＷＩ扫描。计算机测量病变及对照组织（皮下脂肪、肌肉、肺野及噪声）的信号强度，计算其信噪比（ＳＮＲ）和相对信噪比（ＣＮＲ）。结果：２９例支气管肺癌平均信号强度明显高于对照组织（Ｐ＜０．０１），增强后Ｔ１ＷＩ的ＳＮＲ明显高于平扫Ｔ１ＷＩ和Ｔ２ＷＩ；ＣＮＲ（以肌肉为对照）则高于平扫Ｔ１ＷＩ，与Ｔ２ＷＩ相似；与脂肪为参照物则与平扫Ｔ１ＷＩ、Ｔ２ＷＩ相似；以肺野为参照物则与Ｔ１ＷＩ相似，明显高于Ｔ２ＷＩ。结论：支气管肺癌增强后较对照组织有明显的强化；增强后Ｔ１ＷＩ可显著提高ＭＲ的信噪比，改善图像质量。ＭＲ造影剂在胸部有一定的应用价值     

儿童口服自制Gd-DTPA溶液在低场强磁共振胆胰管成像中的应用

目的探讨儿童口服自制Gd-DTPA溶液在低场强（0.35T）磁共振胆胰管成像（MRCP）中的应用价值。方法配制7种不同浓度的含钆溶液各40 ml,设立40 ml温开水为对照组,分析MRCP扫描信号强度,拟定最佳口服浓度。对20例疑有腹部疾病的儿童分别在口服Gd-DTPA溶液前后行常规MRCP扫描。对照口服Gd-DTPA溶液前后图像,系统分析胃十二指肠、胰胆管腔内信号强度并对图片质量评分。结果自制Gd-DTPA溶液选择浓度为1.992 mmol/L。儿童口服80 ml能有效抑制胃十二指肠内液体信号,显著提高MRCP的图像质量（P〈0.01）。结论儿童在低场强MRI上行MRCP检查时,口服浓度为1.992 mmol/L的自制Gd-DTPA溶液能够消除或明显抑制胃肠道内液体的信号,提高儿童低场强MRCP图像质量。