纳米脂质体在肿瘤治疗及影像监测中的应用

纳米脂质体作为抗癌药物、治疗基因载体,用于肿瘤靶向治疗和基因治疗,较传统治疗方法能获得更好的疗效.同时包载显像剂对肿瘤细胞和肿瘤血管生成等进行靶向显像,可为了解肿瘤对治疗的反应提供依据.     

Real-time qualitative MR monitoring of microwave ablation in ex vivo livers

Purpose: Computed tomography (CT) and ultrasound-guided microwave ablations (MWA) are part of the established treatment of liver tumours. In spite of its potential advantages, magnetic resonance (MR) monitoring of MWA did not enter clinical practice because of the lack of compatible devices. The purpose of the current study was to prove the feasibility of real-time qualitative MR monitoring using a new MR-compatible MWA device.

Material and methods: We performed 27 MWA experiments with different durations (5, 10 and 15?min) on an ex vivo bovine liver model using a MR-compatible MWA device. We compared the diameters of the ablation zone as depicted on three T1-based sequences to those of the macroscopic specimen. The volume and the sphericity index of the macroscopic ablation area were calculated in order to characterise the device. Ablation pattern and artefacts on the three sequences were also taken into account.

Results: We obtained high-quality real-time images using all three sequences. The diameters as depicted on the MR sequences slightly overestimated the macroscopic ablation area but correlated significantly in all cases (p?r?=?0.96) and long-axis diameter (r?=?0.87), whereas starVIBE (r?=?0.85; r?=?0.72) and FLASH (r?=?0.75; r?=?0.84) correlated slightly less. Significantly more severe noise artefacts were observed on starVIBE compared to FLASH and VIBE sequences (p?Conclusion: The current ex vivo liver model experiment suggests that real-time qualitative MR monitoring of MWA is feasible. Further research using in vivo and human models are recommended.     

Utilisation of MR spectroscopy and diffusion weighted imaging in predicting and monitoring of breast cancer response to chemotherapy

Neoadjuvant chemotherapy (NACT) is the standard treatment option for breast cancer as more data shows that pathologic complete response (pCR) after NACT correlates with improved prognosis. MRI is accepted as the best imaging modality for evaluating the response to NACT in many studies as compared with clinical examination and other imaging modalities. In vivo magnetic resonance spectroscopy (MRS) and diffusion‐weighted imaging (DWI) studies have both emerged as potential tools to provide early response indicators based on the changes in the metabolites and the apparent diffusion coefficient (ADC) respectively. In this review article, we aim to discuss the strength and limitations of MRS and DWI in monitoring of early response breast cancer to NACT.     

Non-invasive monitoring of hepatocellular carcinoma in transgenic mouse with bioluminescent imaging

A small animal imaging system for hepatocellular carcinoma (HCC)-specific reporter gene expression will enable monitoring of carcinogenesis or therapeutic intervention in vivo. Transgenic mouse was developed in which firefly luciferase (fLuc) expression was controlled by the AFP enhancer/promoter. The bioluminescent signals of the transgenic neonates were strong at their liver region and decreased after birth. Bioluminescent imaging (BLI) of a transgenic mouse treated with N-nitrosodiethylamine revealed distinct fLuc activity in the liver and an increased pattern with time. The transgenic mouse model can be used to monitor AFP producing HCC by a chemical carcinogen in a live animal by BLI.     

乳腺癌放射治疗真空垫固定摆位误差分析及优势

背景与目的:目前国内乳腺癌放射治疗使用乳腺托架固定摆位的精度较高,但许多单位没有大孔径CT,因此乳腺托架无法使用。该研究旨在探讨在没有大孔径CT时,乳腺癌术后患者在放射治疗时使用真空垫固定的摆位误差和产生原因。方法:选取2011年11月—2012年2月期间上海交通大学医学院仁济医院放疗科收治的30例乳腺癌术后患者,接受放射治疗并用真空垫固定进行CT定位,使用医科达Precise型加速器上兆伏级电子射野影像系统(electron portal imaging device,EPID)对患者实施锁骨上野和胸壁切线野拍片,并与治疗计划中的射野位置对比验证,统计出X、Y、Z轴3个方向的平均误差及最大误差。结果:X、Y、Z轴平均误差分别为(1.61±1.12)、(1.56±1.12)和(1.50±0.9)mm。结论:乳腺癌术后患者使用真空负压成型垫固定,能保证摆位的精度,在没有固定架条件下实用性高。     

An isocenter position verification device for electronic portal imaging: physical and dosimetrical characteristics

The physical and dosimetrical characteristics of a device, designed to visualize the isocenter position on electronic portal images, were examined. The device, to be mounted on the gantry head of the accelerator, containing five spheric lead markers, was designed in order to visualize the isocenter position on portal images. A quality control device was designed to check the reliability of this technique. The disturbance of the dose distribution by the markers was studied with gel dosimetry. The use of markers resulted in a precise and accurate method to visualize the isocenter on portal images. A maximum underdosage of 11%, due to attenuation by the markers, was observed. The use of markers to visualize the isocenter position on portal images, is a fast and reliable method when analyzing patient setup errors with online electronic portal imaging.     

Detection of fiducial gold markers for automatic on-line megavoltage position verification using a marker extraction kernel (MEK)

Purpose: In this study automatic detection of implanted gold markers in megavoltage portal images for on-line position verification was investigated.

Methods and Materials: A detection method for fiducial gold markers, consisting of a marker extraction kernel (MEK), was developed. The detection success rate was determined for different markers using this MEK. The localization accuracy was investigated by measuring distances between markers, which were fixed on a perspex template. In order to generate images comparable to images of patients with implanted markers, this template was placed on the skin of patients before the start of the treatment. Portal images were taken of lateral prostate fields at 18 MV within 1–2 monitor units (MU).

Results: The detection success rates for markers of 5 mm length and 1.2 and 1.4 mm diameter were 0.95 and 0.99 respectively when placed at the beam entry and 0.39 and 0.86 when placed at the beam exit. The localization accuracy appears to be better than 0.6 mm for all markers.

Conclusion: Automatic marker detection with an acceptable accuracy at the start of a radiotherapy fraction is feasible. Further minimization of marker diameters may be achieved with the help of an a-Si flat panel imager and may increase the clinical acceptance of this technique.     

Experience and new prospects of PET imaging for ion beam therapy monitoring

Pioneering investigations on the usage of positron-emission-tomography (PET) for the monitoring of ion beam therapy with light (protons, helium) and heavier (stable and radioactive neon, carbon and oxygen) ions started shortly after the first realization of planar and tomographic imaging systems, which were able to visualize the annihilation of positrons resulting from irradiation induced or implanted positron emitting nuclei. And while the first clinical experience was challenged by the utilization of instrumentation directly adapted from nuclear medicine applications, new detectors optimized for this unconventional application of PET imaging are currently entering the phase of (pre)clinical testing for more reliable monitoring of treatment delivery during irradiation. Moreover, recent advances in detector technologies and beam production open several new exciting opportunities which will not only improve the performance of PET imaging under the challenging conditions of in-beam applications in ion beam therapy, but will also likely expand its field of application. In particular, the combination of PET and Compton imaging can enable the most efficient utilization of all possible radiative emissions for both stable and radioactive ion beams, while positronium lifetime imaging may enable probing new features of the underlying tumour and normal tissue environment. Thereby, PET imaging will not only provide means for volumetric reconstruction of the delivered treatment and in-vivo verification of the beam range, but can also shed new insights for biological optimization of the treatment or treatment response assessment.     

Pelvic hemangiopericytoma: the role of diffusion weighted imaging in targeting the biopsy site and in monitoring the tumour response to radiotherapy

BACKGROUND: Despite advances in imaging, the accurate characterization of soft tissue tumours remains a challenging task. Furthermore, the interpretation of post treatment changes and evaluation of tumour response to therapy is another complicating issue regarding soft tissue tumour imaging. CASE REPORT.: Herein, a patient with a pelvic hemangiopericytoma, by whom different diagnostic imaging methods were used, is presented. CONCLUSIONS: Diffusion weighted imaging (DWI) might provid useful information in guiding biopsy and enabled monitoring of the radiation therapy results.     

Convection-enhanced delivery of maghemite nanoparticles: Increased efficacy and MRI monitoring

Convection-enhanced drug delivery (CED) is a novel approach to delivering drugs into brain tissue. Drugs are delivered continuously via a catheter, enabling large volume distributions of high drug concentrations with minimum systemic toxicity. Previously we demonstrated that CED formation/extent of small molecules may be significantly improved by increasing infusate viscosities. In this study we show that the same methodology can be applied to monodispersed maghemite nanoparticles (MNPs). For this purpose we used a normal rat brain model and performed CED of MNPs over short infusion times. By adding 3% sucrose or 3%-6% polyethylene glycol (PEG; molecular weight 400) to saline containing pristine MNPs, we increased infusate viscosity and obtained increased CED efficacy. Further, we show that CED of dextran-coated MNPs (dextran-MNPs) resulted in increased efficacy over pristine MNPs (p < 0.007). To establish the use of MRI for reliable depiction of MNP distribution, CED of fluorescent dextran-MNPs was performed, demonstrating a significant correlation between the distributions as depicted by MRI and spectroscopic images (r(2) = 0.74, p < 0.0002). MRI follow-up showed that approximately 80%-90% of the dextran-MNPs were cleared from the rat brain within 40 days of CED; the rest remained in the brain for more than 4 months. MNPs have been tested for applications such as targeted drug delivery and controlled drug release and are clinically used as a contrast agent for MRI. Thus, combining the CED method with the advantages of MNPs may provide a powerful tool to treat and monitor brain tumors.     

晚期非小细胞肺癌疗效监测的研究进展

晚期非小细胞肺癌（NSCLC）具有高度异质性,其临床治疗强调个体化和综合性。随着肺癌分子机制的深入研究和不断阐明,以及分子靶向、单克隆抗体、免疫制剂和抗血管生成等多种新型药物的临床应用,晚期NSCLC患者疗效评价已不再局限于基于瘤体大小变化的实体瘤疗效评价标准,基于蛋白质和核酸水平的分子影像学、分子病理学和液体活检将是晚期NSCLC患者疗效监测新的发展方向。     

基于Her-2靶向成像技术实时评价乳腺癌靶向治疗效果的研究进展

乳腺窟针对Her-2靶向治疗已得到广泛应用,实时有效预测与动态监测靶向治疗效果至关重要。传统方法通过治疗前检测肿瘤组织Her-2表达水平,治疗后观察肿瘤形态学改变来选择治疗方案与评价治疗效果。这一方法用于早期预测和评估治疗效果的能力有限。分子影像学的发展为解决这一难题带来了新的契机。现针对靶向Her-2基因通过分子成像技术实时评价乳腺癌靶向治疗效果的研究进展做一综述。     

Electronic portal images (EPIs) based position verification for the breast simultaneous integrated boost (SIB) technique

Background and purpose

To develop a method based on electronic portal images (EPIs) for the position verification of breast cancer patients that are treated with a simultaneous integrated boost (SIB) technique.

Method

3D setup errors of the breast outline and the thoracic wall were determined from EPIs of the tangential treatment fields and anterior posterior (AP) verification field. The method was verified with repeated CT scans of 38 patients with an average setup error larger than 5 mm.

Result

The 3D position deviation of the boost volume can best be determined from the position deviation of the breast outline in the ventrodorsal direction and the thoracic wall in the lateral and longitudinal directions from the tangential and AP EPIs. The method gives an average overestimation of the deviation of the boost volume in the ventrodorsal, lateral and longitudinal directions by 28%, 20% and 6%, respectively and an average underestimation of the deviation of the whole breast by 32%, 17% and 39%.

Conclusions

The described method is superior to using tangential EPIs only and is recommended for position verification of breast cancer patients that are treated with a SIB technique if no Cone beam CT (CBCT) or fiducial markers can be used.     

Radiopharmaceuticals in the elderly cancer patient: Practical considerations,with a focus on prostate cancer therapy: A position paper from the International Society of Geriatric Oncology Task Force

Molecular imaging using radiopharmaceuticals has a clear role in visualising the presence and extent of tumour at diagnosis and monitoring response to therapy. Such imaging provides prognostic and predictive information relevant to management, e.g. by quantifying active tumour mass using positron emission tomography/computed tomography (PET/CT). As these techniques require only pharmacologically inactive doses, age and potential frailty are generally not important. However, this may be different for therapy involving radionuclides because the radiation can impact normal bodily function (e.g. myelosuppression). Since the introduction of Iodine-131 as a targeted therapy in thyroid cancer, several radiopharmaceuticals have been widely used. These include antibodies and peptides targeting specific epitopes on cancer cells. Among therapeutic bone seeking agents, radium-223 (²²³Ra) stands out as it results in survival gains in patients with castration-resistant prostate cancer and symptomatic bone metastases. The therapeutic use of radiopharmaceuticals in elderly cancer patients specifically has received little attention. In elderly prostate cancer patients, there may be advantages in radionuclides' ease of use and relative lack of toxicity compared with cytotoxic and cytostatic drugs. When using radionuclide therapies, close coordination between oncology and nuclear medicine is needed to ensure safe and effective use. Bone marrow reserve has to be considered. As most radiopharmaceuticals are cleared renally, dose adjustment may be required in the elderly. However, compared with younger patients there is less, if any, concern about adverse long-term radiation effects such as radiation-induced second cancers. Issues regarding the safety of medical staff, care givers and the wider environment can be managed by current precautions.     

应用EPID代替胶片法对MLC的质控研究

目的 研究EPID代替胶片对加速器MLC的质控方法并探讨其在任意机架角度下的可行性。方法 采用RIT113软件对EPID影像和EBT3胶片影像数据进行分析。以EBT3胶片射野边缘50%等剂量曲线位置定义MLC叶片实际位置,在同一射野条件下EPID影像数据中找到MLC叶片实际位置所对应百分剂量值,从而完成EPID到EBT3胶片的替代过程。结果 加速器机架角0°时,以EBT3胶片确定的MLC叶片位置处EPID影像对应的期望百分剂量值为44%,最大MLC位置误差为0.12 mm。任意机架角度时,EPID影像数据通过与0°结果做距离一致性分析比对,半径为0.5 mm时所有像素点均通过。结论 采用EPID代替胶片对加速器MLC叶片到位质控方法可行,且其精度满足临床要求并适用于任意机架角的测量,具有广泛推广和借鉴意义。     

Brain and whole-body FDG-PET in diagnosis,treatment monitoring and long-term follow-up of primary CNS lymphoma

Background

Positron emission tomography (PET) with F-18-labeled fluorodeoxyglucose (FDG) provides remarkable accuracy in detection, treatment monitoring and follow-up of systemic malignant lymphoma. Its value in the management of patients with primary central nervous system lymphoma (PCNSL) is less clear.

Patients and methods

In a prospective trial, 42 FDG-PET examinations were performed in ten immunocompetent patients with newly diagnosed or recurrent PCNSL before and repeatedly during and after the treatment. Brain and whole body FDG-PET were compared to brain MRI and extra-cerebral CT, respectively.

Results

Before the treatment, 6 of 10 patients had congruent findings on FDG-PET and MRI of the brain. Three patients had lesions on brain MRI, not detected by FDG-PET. One patient had additional FDG-PET positive lesions inconspicuous in MRI. The follow-up suggested FDG-PET to be false positive in these lesions. After the treatment, brain PET was in agreement with MRI in 6 of 8 patients. In the remaining 2 patients there were persistent lesions in brain MRI whereas FDG-uptake was reduced to normal values. In the long-term follow-up of 5 patients (63–169 weeks), 3 patients retained normal in both PET and MRI. In 2 patients a new focal pathologic FDG-uptake was detected 69 and 52 weeks after the end of the treatment. In one of these patients, recurrence was confirmed by MRI not until 9 weeks after PET.

Conclusions

Brain FDG-PET may contribute valuable information for the management of PCNSL, particularly in the assessment of the treatment response. Integration of FDG-PET into prospective interventional trials is warranted to investigate prognostic and therapeutic implications.     

In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring

Background:

In patients with advanced ovarian cancer (OvCa), microscopic residual tumour nodules that remain after surgical debulking frequently escape detection by current treatment assessment methods and lead to disease recurrence. The aim of this study was to evaluate the use of high-resolution fibre-optic fluorescence imaging of the clinically approved photodynamic therapy (PDT) agent benzoporphyin-derivative monoacid ring A (BPD-MA) for detection of microscopic OvCa and for monitoring treatment response.

Methods:

Our fluorescence microendoscope consists of a flexible imaging fibre coupled to a custom epi-fluorescence system optimised for imaging BPD-MA, which, after a single administration, serves as both an imaging agent and a light-activated therapeutic agent. After characterisation in an in vitro OvCa 3D model, we used the flexible imaging fibre to minimally invasively image the peritoneal cavity of a disseminated OvCa murine model using BPD-MA administered intraperitoneally (i.p.). To evaluate longitudinal changes in response to treatment, we compared sets of images obtained before and after PDT with those from untreated mice imaged at the same time points.

Results:

By comparison with histopathology, we report an 86% sensitivity for tumour detection in vivo using the microendoscope. Using a custom routine to batch process-image data in the monitoring study, treated mice exhibited an average decrease of 58.8% in tumour volumes compared with an increase of 59.3% in untreated controls (P<0.05).

Conclusions:

Our findings indicate the potential of this approach as a reporter of treatment outcome that could aid in the rational design of strategies to mitigate recurrent OvCa.     

基于EPID和EBT3胶片剂量计对动态MLC叶片到位精度检测研究

目的 建立一种使用EPID和EBT3胶片剂量计进行动态MLC叶片到位精度的快速准确检测方法。方法 美国瓦里安6 MV加速器的固定机架角和准直器角度为0°,共设计11个MLC以滑窗方式运行的射野,每个射野由一组相同宽度的窄条野组成,窄条野的宽度为1~10 mm,窄条野之间的间距为2 cm。使用EPID、EBT3胶片剂量计作为测量工具,刻度设计窄条野宽度(带宽)与测量带宽的半高宽的关系。以同样方式设计一带宽为5 mm射野,并在不同位置设计几处MLC叶片偏差,通过EPID、EBT3分析MLC叶片到位精度。结果 当设计带宽>4 mm时,可很好地线性拟合设计带宽与实测带宽的半高宽。EPID检测带宽、峰值间距、MLC叶片位置的精度分别为±0.2、±0.1、±0.1 mm,EBT3检测的分别为±0.3、±0.2、±0.2 mm。结论 提供了一种使用EPID或EBT3胶片剂量计快速检测MLC实际到位精度的方法,为MLC的QA提供帮助。