Use of magnetic resonance imaging to assess blood-brain/blood-glioma barrier opening during conformal radiotherapy.

PURPOSE: For chemotherapy to act synergistically and safely with radiation against high-grade gliomas, drugs must pass the endothelial junctions of the blood-tumor barrier (BTB) to reach all tumor cells, and should not pass the blood-brain barrier (BBB) to cause toxicity to normal brain. The objective of this study was to assess BBB/BTB status using magnetic resonance imaging (MRI) during a course of radiotherapy of high-grade gliomas. PATIENTS AND METHODS: Sixteen patients with grade 3 or 4 supratentorial malignant glioma receiving conformal radiotherapy (RT) underwent contrast-enhanced MRI before, during, and after completion of RT. A gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) uptake index was analyzed with respect to the tumor and RT dose received. RESULTS: In the nonenhanced tumor region, contrast uptake increased significantly after the receipt of approximately 10 Gy (P < .01), and reached a maximum after the receipt of approximately 30 Gy. In the initially contrast-enhanced tumor region, contrast uptake decreased over the course of RT and became significant after completion of RT in patients without progressive disease. The healthy brain showed only nonsignificant changes during and after irradiation. CONCLUSION: Contrast MRI reveals increases in Gd-DTPA uptake in the initially nonenhanced tumor region but not in the remaining brain during the course of RT, suggesting opening of the BTB. This finding suggests that the effect of conformal radiation is more selective on the BTB than the BBB, and there may be a window extending from 1 week after the initiation of radiotherapy to 1 month after the completion of treatment during which a pharmaceutical agent has maximum access to high-grade gliomas.     

In vivo and ex vivo assessment of the blood brain barrier integrity in different glioblastoma animal models

Blood brain barrier (BBB) disruption is used (pre)clinically as a measure for brain tumor malignancy and grading. During treatment it is one of the parameters followed rigorously to assess therapeutic efficacy. In animal models, both invasive and non-invasive methods are used to determine BBB disruption, among them Evans blue injection prior to sacrifice and T1-weighted magnetic resonance imaging (MRI) post contrast injection. In this study, we have assessed the BBB integrity with the methods mentioned above in two experimental high grade glioma models, namely the GL261 mouse glioblastoma model and the Hs683 human oligodendroglioma model. The GL261 model showed clear BBB integrity loss with both, contrast-enhanced (CE) MRI and Evans blue staining. In contrast, the Hs683 model only displayed BBB disruption with CE-MRI, which was not evident on Evans blue staining, indicating a limited BBB disruption. These results clearly indicate the importance of assessing the BBB integrity status using appropriate methods. Especially when using large therapeutic molecules that have difficulties crossing the BBB, care should be taken with the appropriate BBB disruption assessment studies.     

Vascular endothelial growth factor-A determines detectability of experimental melanoma brain metastasis in GD-DTPA-enhanced MRI

We have previously shown that the dense vascular network in mouse brain allows for growth of human melanoma xenografts (Mel57) by co-option of preexisting vessels. Overexpression of recombinant vascular endothelial growth factor-A (VEGF-A) by such xenografts induced functional and morphologic alterations of preexisting vessels. We now describe the effects of VEGF-A expression on visualization of these brain tumors in mice by magnetic resonance imaging (MRI), using gadolinium diethylenetriaminepenta-acetic acid (Gd-DTPA) and ultra small paramagnetic iron oxide particles (USPIO) as contrast agents. Brain lesions derived from (mock-transfected) Mel57 cells were undetectable in MRI after Gd-DTPA injection. However, the majority of such lesions became visible after injection of USPIO, due to the lower vascular density in the lesions as compared to the surrounding parenchyma. In contrast, VEGF-A-expressing lesions were visualized using Gd-DTPA-enhanced MRI by a rapid circumferential enhancement, due to leaky peritumoral vasculature. USPIO-enhanced MRI of these tumors corroborated the immunohistochemic finding that peritumorally located, highly irregular and dilated vessels were present, while intratumoral vessel density was low. Our study shows that VEGF-A is a key factor in imaging of brain neoplasms. Our data also demonstrate that, at least in brain, blood-pool agent-enhanced MRI may be a valuable diagnostic tool to detect malignancies that are not visible on Gd-DTPA-enhanced MRI. Furthermore, the involvement of VEGF-A in MRI visibility suggests that care must be taken with MRI-based evaluation of antiangiogenic therapy, as anti-VEGF treatment might revert a tumor to a co-opting phenotype, resulting in loss of contrast enhancement in MRI.     

Editor's choice: Current standards and new concepts in MRI and PET response assessment of antiangiogenic therapies in high-grade glioma patients

Despite multimodal treatment, the prognosis of high-grade gliomas is grim. As tumor growth is critically dependent on new blood vessel formation, antiangiogenic treatment approaches offer an innovative treatment strategy. Bevacizumab, a humanized monoclonal antibody, has been in the spotlight of antiangiogenic approaches for several years. Currently, MRI including contrast-enhanced T1-weighted and T2/fluid-attenuated inversion recovery (FLAIR) images is routinely used to evaluate antiangiogenic treatment response (Response Assessment in Neuro-Oncology criteria). However, by restoring the blood–brain barrier, bevacizumab may reduce T1 contrast enhancement and T2/FLAIR hyperintensity, thereby obscuring the imaging-based detection of progression. The aim of this review is to highlight the recent role of imaging biomarkers from MR and PET imaging on measurement of disease progression and treatment effectiveness in antiangiogenic therapies. Based on the reviewed studies, multimodal imaging combining standard MRI with new physiological MRI techniques and metabolic PET imaging, in particular amino acid tracers, may have the ability to detect antiangiogenic drug susceptibility or resistance prior to morphological changes. As advances occur in the development of therapies that target specific biochemical or molecular pathways and alter tumor physiology in potentially predictable ways, the validation of physiological and metabolic imaging biomarkers will become increasingly important in the near future.     

Magnetic Resonance Imaging of Ethyl-nitrosourea-induced Rat Gliomas: A Model for Experimental Therapeutics of Low-grade Gliomas

Human low-grade gliomas represent a population of brain tumors that remain a therapeutic challenge. Preclinical evaluation of agents, to test their preventive or therapeutic efficacy in these tumors, requires the use of animal nobreak models. Spontaneous gliomas develop in models of chemically induced carcinogenesis, such as in the transplacental N-ethyl-N-nitrosourea (ENU) rat model. However, without the ability to detect initial tumor formation, multiplicity or to measure growth rates, it is difficult to test compounds for their interventional or preventional capabilities. In this study Fisher-334 rats, treated transplacentally with ENU, underwent magnetic resonance imaging (MRI) examination in order to evaluate this approach for detection of tumor formation and growth. ENU-induced intracranial cerebral tumors were first observable in T2-weighted images beginning at 4 months of age and grew with a mean doubling time of 0.487 ± 0.112 months. These tumors were found histologically to be predominately mixed gliomas. Two therapeutic interventions were evaluated using MRI, vitamin A (all-trans retinol palmitate, RP), as a chemopreventative agent and the anti-angiogenic drug SU-5416. RP was found to significantly delay the time to first tumor observation by one month (P = 0.05). No differences in rates of tumor formation or growth rates were observed between control and RP-treated groups. MRI studies of rats treated with SU-5416 resulted in reduction in tumor growth rates compared to matched controls. These results show that MRI can be used to provide novel information relating to the therapeutic efficacy of agents against the ENU-induced tumor model.     

Dual kinin B1 and B2 receptor activation provides enhanced blood–brain barrier permeability and anticancer drug delivery into brain tumors

The low permeability of the BBB is largely responsible for the lack of effective systemic chemotherapy against primary and metastatic brain tumors. Kinin B1R and B2R have been shown to mediate reversible tumor-selective BBB disruption in preclinical animal models. We investigated whether co-administration of two novel potent kinin B1R and B2R agonists offers an advantage over administering each agonist alone for enhancing BBB permeability and tumor targeting of drugs in the malignant F98 glioma rat model. A new covalent kinin heterodimer that equally stimulates B1R and B2R was also constructed for the purpose of our study. We found that co-administration of B1R and B2R agonists, or alternatively administration of the kinin heterodimer more effectively delivered the MRI contrast agent Gd-DTPA and the anticancer drug carboplatin to brain tumors and surrounding tissues than the agonists alone (determined by MRI and ICP-MS methods). Importantly, the efficient delivery of carboplatin by the dual kinin receptor targeting on the BBB translated into increased survival of glioma-bearing rats. Thus, this report describes a potential strategy for maximizing the brain bioavailability and therapeutic efficacy of chemotherapeutic drugs.     

Magnetic resonance imaging of brain tumors

Magnetic resonance imaging (MRI) has been applied to the diagnosis of brain tumors very widely and MRI is now replacing computed tomography (CT). One of the most important advantages of MRI is influence of multiple tissue and machine parameters on the signal intensities. In addition, capability of imaging in various planes and multislices is another advantage for the brain tumor diagnosis. The coronal image is important when the abnormal side can be compared with the normal side and midline lesions can be easily diagnosed with sagittal imaging. Transverse imaging is important when comparison is made with CT. Many brain tumors show increased signal intensity on T2-weighted images and decreased signal intensity on T1-weighted images and decreased signal intensity on T1-weighted images. The difference of signal intensity in various brain tumors including glioma, meningioma and other important tumors are discussed. MRI is superior to CT in many brain tumors, but poor delineation of calcification and hemorrhage is a disadvantage of MRI.     

Noninvasive detection of temozolomide in brain tumor xenografts by magnetic resonance spectroscopy

Poor drug delivery to brain tumors caused by aberrant tumor vasculature and a partly intact blood-brain barrier (BBB) and blood-brain tumor barrier (BTB) can significantly impair the efficacy of chemotherapy. Determining drug delivery to brain tumors is a challenging problem, and the noninvasive detection of drug directly in the tumor can be critically important for accessing, predicting, and eventually improving effectiveness of therapy. In this study, in vivo magnetic resonance spectroscopy (MRS) was used to detect an anticancer agent, temozolomide (TMZ), in vivo in murine xenotransplants of U87MG human brain cancer. Dynamic magnetic resonance imaging (MRI) with the low-molecular-weight contrast agent, gadolinium diethylenetriaminepentaacetic acid (GdDTPA), was used to evaluate tumor vascular parameters. Carbon-13-labeled TMZ ([¹³C]TMZ, 99%) was intraperitoneally administered at a dose of ∼140 mg/kg (450 mg/m², well within the maximal clinical dose of 1000 mg/m² used in humans) during the course of in vivo MRS experiments. Heteronuclear multiple-quantum coherence (HMQC) MRS of brain tumors was performed before and after i.p. administration of [¹³C]TMZ. Dynamic MRI experiments demonstrated slower recovery of MRI signal following an intravenous bolus injection of GdDTPA, higher vascular flow and volume obtained by T*₂-weighted MRI, as well as enhanced uptake of the contrast agent in the brain tumor compared with normal brain detected by T₁-weighted MRI. These data demonstrate partial breakdown of the BBB/BTB and good vascularization in U87MG xenografts. A [¹³C]TMZ peak was detected at 3.9 ppm by HMQC from a selected volume of about 0.15 cm³ within the brain tumor with HMQC pulse sequences. This study clearly demonstrates the noninvasive detection of [¹³C]TMZ in xenografted U87MG brain tumors with MRS. Noninvasive tracking of antineoplastic agents using MRS can have a significant impact on brain tumor chemotherapy.     

Tissue concentration of systemically administered antineoplastic agents in human brain tumors

The blood–brain-barrier (BBB) limits the penetration of many systemic antineoplastic therapies. Consequently, many agents may be used in clinical studies and clinical practice though they may not achieve therapeutic levels within the tumor. We sought to compile the currently available human data on antineoplastic drug concentrations in brain and tumor tissue according to BBB status. A review of the literature was conducted for human studies providing concentrations of antineoplastic agents in blood and metastatic brain tumors or high-grade gliomas. Studies were considered optimal if they reported simultaneous tissue and blood concentration, multiple sampling times and locations, MRI localization, BBB status at sampling site, tumor histology, and individual subject data. Twenty-Four studies of 19 compounds were included. These examined 18 agents in contrast-enhancing regions of high-grade gliomas, with optimal data for 2. For metastatic brain tumors, adequate data was found for 9 agents. Considerable heterogeneity was found in the measurement value, tumor type, measurement timing, and sampling location within and among studies, limiting the applicability of the results. Tissue to blood ratios ranged from 0.054 for carboplatin to 34 for mitoxantrone in high-grade gliomas, and were lowest for temozolomide (0.118) and etoposide (0.116), and highest for mitoxantrone (32.02) in metastatic tumors. The available data examining the concentration of antineoplastic agents in brain and tumor tissue is sparse and limited by considerable heterogeneity. More studies with careful quantification of antineoplastic agents in brain and tumor tissue is required for the rational development of therapeutic regimens.     

Magnetic resonance imaging determination of tumor grade and early response to temozolomide in a genetically engineered mouse model of glioma.

PURPOSE: The median survival for patients diagnosed with glioblastoma multiforme, the most common type of brain tumor, is less than 1 year. Animal glioma models that are more predictive of therapeutic response in human patients than traditional models and that are genetically and histologically accurate are an unmet need. The nestin tv-a (Ntv-a) genetically engineered mouse spontaneously develops glioma when infected with ALV-A expressing platelet-derived growth factor, resulting in autocrine platelet-derived growth factor signaling. EXPERIMENTAL DESIGN: In the Ntv-a genetically engineered mouse model, T2-weighted and T1-weighted, contrast-enhanced magnetic resonance images were correlated with histology, glioma grade (high or low), and survival. Magnetic resonance imaging (MRI) was therefore used to enroll mice with high-grade gliomas into a second study that tested efficacy of the current standard of care for glioma, temozolomide (100 mg/kg qdx5 i.p., n=13). RESULTS: The Ntv-a model generated a heterogeneous group of gliomas, some with high-grade growth rate and histologic characteristics and others with characteristics of lower-grade gliomas. We showed that MRI could be used to predict tumor grade and survival. Temozolomide treatment of high-grade tv-a gliomas provided a 14-day growth delay compared with vehicle controls. Diffusion MRI measurement of the apparent diffusion coefficient showed an early decrease in cellularity with temozolomide, similar to that observed in humans. CONCLUSIONS: The use of MRI in the Ntv-a model allows determination of glioma grade and survival prediction, distribution of mice with specific tumor types into preclinical trials, and efficacy determination both by tumor growth and early apparent diffusion coefficient response.     

The efficacy of MRI with ultrasmall superparamagnetic iron oxide particles (USPIO) in head and neck cancers

BACKGROUND: The objective was to evaluate the diagnostic accuracy of ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) compared to plain MRI in patients with a clinical N+ neck using histology as a gold standard. MATERIALS AND METHODS: Twenty-eight patients underwent unenhanced and USPIO-enhanced MRI using T1-weighted spin echo (SE) sequences and high resolution Turbo-Spin-Echo (TSE) T2-weighted sequences, as well as T2-weighted Gradient Echo (GE) sequences in axial and sagittal slice orientation. The signal intensity (SI) decrease was measured by a region of interest evaluation and visual analysis was performed. RESULTS: Histopathological evaluation of 363 lymph nodes revealed 34 as metastatic. USPIO MRI detected 28 metastases (sensitivity 82.3%) and 329 non-metastatic lymph nodes (specificity 100%). Regarding lymph node size, USPIO MRI was correct in all patients who underwent surgery. One lymph node with microinfiltration of tumor cells was detected by USPIO MRI. CONCLUSION: There were no side-effects during or after application of the contrast agent. This study confirms the efficacy of MRI with USPIO in patients with head and neck cancer. USPIO-enhanced MRI could have an important effect on surgery planning. Because of its high specificity, USPIO-enhanced MRI seems to be a diagnostic modality able to differentiate borderline-sized lymph nodes.     

Intraoperative use of an open mid-field MR scanner in the surgical treatment of cerebral gliomas

The aim of the present study was to evaluate the effectiveness of intraoperative MRI guidance in achieving more gross-total resection in case of primary brain tumors. We studied 12 patients with low-grade glioma and 19 patients with high-grade glioma who underwent surgery within a vertically open 0.5 T MR system. After initial imaging, the resection was stopped at the point in which the neurosurgeon considered the resection complete by viewing the operation field. At this time, intraoperative MRI was repeated ("first control") to identify any residual tumor. Areas of tumor-suspected tissue were localized and resected, with the exception of tissue adjacent to eloquent areas. Final imaging was carried out before closing the craniotomy. Comparison of "first control" and final imaging revealed a decrease of residual tumor volume from 32% to 4.3% in low-grade gliomas, and from 29% to 10% in high-grade gliomas. Intraoperative MRI allows a clear optimization of microsurgical resection of both low-grade and high-grade gliomas.     

Single cell molecular recognition of migrating and invading tumor cells using a targeted fluorescent probe to receptor PTPmu

Detection of an extracellular cleaved fragment of a cell–cell adhesion molecule represents a new paradigm in molecular recognition and imaging of tumors. We previously demonstrated that probes that recognize the cleaved extracellular domain of receptor protein tyrosine phosphatase mu (PTPmu) label human glioblastoma brain tumor sections and the main tumor mass of intracranial xenograft gliomas. In this article, we examine whether one of these probes, SBK2, can label dispersed glioma cells that are no longer connected to the main tumor mass. Live mice with highly dispersive glioma tumors were injected intravenously with the fluorescent PTPmu probe to test the ability of the probe to label the dispersive glioma cells in vivo. Analysis was performed using a unique three‐dimensional (3D) cryo‐imaging technique to reveal highly migratory and invasive glioma cell dispersal within the brain and the extent of colabeling by the PTPmu probe. The PTPmu probe labeled the main tumor site and dispersed cells up to 3.5 mm away. The cryo‐images of tumors labeled with the PTPmu probe provide a novel, high‐resolution view of molecular tumor recognition, with excellent 3D detail regarding the pathways of tumor cell migration. Our data demonstrate that the PTPmu probe recognizes distant tumor cells even in parts of the brain where the blood–brain barrier is likely intact. The PTPmu probe has potential translational significance for recognizing tumor cells to facilitate molecular imaging, a more complete tumor resection and to serve as a molecular targeting agent to deliver chemotherapeutics to the main tumor mass and distant dispersive tumor cells.     

MRI of mouse models for gliomas shows similarities to humans and can be used to identify mice for preclinical trials

Magnetic resonance imaging (MRI) has been utilized for screening and detecting brain tumors in mice based upon their imaging characteristics appearance and their pattern of enhancement. Imaging of these tumors reveals many similarities to those observed in humans with identical pathology. Specifically, high-grade murine gliomas have histologic characteristics of glioblastoma multiforme (GBM) with contrast enhancement after intravenous administration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), implying disruption of the blood-brain barrier in these tumors. In contrast, low-grade murine oligodendrogliomas do not reveal contrast enhancement, similar to human tumors. MRI can be used to identify mice with brain neoplasms as inclusion criteria in preclinical trials.     

弥散张量成像在脑肿瘤中的应用

目的 探讨脑肿瘤弥散张量成像(DTI)的特点及其在脑肿瘤中的诊断和鉴别诊断价值.方法 对39例经病理证实的脑肿瘤患者(脑膜瘤10例,胶质瘤17例,转移瘤12例),采用PhilipsAchieva 1.5 T磁共振行常规MRI和DTI,在工作站上重建部分各向异性(FA)图、表观弥散系数(ADC)图和三维白质纤维束图,选择...     

CT灌注成像在脑部肿瘤患者诊断中的应用

目的:探讨CT灌注成像在脑部肿瘤患者中的诊断效果。方法:取2015年5月至2016年9月首都医科大学附属北京世纪坛医院收治脑部肿瘤患者43例,均行常规CT扫描、CT灌注成像及增强扫描,将获得的数据、图像采用CT工作站Perfusion3软件进行处理,获得患者脑血流量（CBF）、血容量（CBV）、对比剂平均通过时间（MTT）。结果:43例患者最终经CT灌注成像检查得到确诊,患者中,28例胶质瘤（占65.12%）、11例脑膜瘤（占25.58%）、2例转移瘤（占4.65%）、2例其他（占4.65%）;脑部CT灌注成像中转移瘤病灶处、健侧CBF值,高于胶质瘤、脑膜瘤及其他（P<0.05）;脑膜瘤病灶处、健侧CBF值,高于胶质瘤（P<0.05）;脑部肿瘤中转移瘤病灶处、健侧血容量、对比剂平均通过时间,高于胶质瘤、脑膜瘤（P<0.05）;脑膜瘤病灶处、健侧血容量、对比剂平均通过时间,高于胶质瘤（P<0.05）。结论:脑部肿瘤患者采用CT灌注成像诊断能了解脑肿瘤部位血流状态、肿瘤血管功能,指导临床治疗,值得推广应用。     

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.     

磁共振功能成像在脑胶质瘤侵袭性行为评价中的作用

脑胶质瘤的侵袭常沿着有髓神经纤维和血管基底膜途径进行。MR功能成像包括MRS、PWI和DWI．具有一定的分子成像的能力。MRS代谢物浓度变化可以明确瘤体和瘤周的代谢物变化。Cho／Cr值自近瘤周区向远瘤周区有逐渐降低的趋势．而NAA／Cr则有升高趋势．符合胶质瘤沿白质纤维自近向远侵袭性生长的特点。MRI灌注成像rCBV对胶质瘤分级的预测具有一定价值。MRI弥散成像通过反映组织内水分子的扩散特性反映脑内肿瘤的病理变化,常以扩散张量成（DTI）、表观扩散系数（ADC）和白质纤维柬追踪~（V13来间接反映胶质瘤的生物学侵袭性特点。MR功能成像在评价脑胶质瘤侵袭性上具有一定价值,临床医生应把传统MRI与多种功能成像技术联合应用来提高MRI对胶质瘤侵袭性的认识。     

利用T1加权动态对比度增强灌注MRI技术确定脑胶质瘤放疗靶区的研究

目的 探讨利用T1加权动态对比度增强灌注MRI (DCEPMRI)技术在放疗中确定脑胶质瘤临床靶区的研究。方法 对 28例脑胶质瘤患者团注顺磁性造影剂Gd-DTPA后,采集其T1加权DCEPMRI,对获得图像用改进的Tofts-Kermode两室分析模型和反卷积法进行处理分析得到微血管通透性相关定量参数K_trans值及图,并比较最大病灶区所在层面常规增强MRI与T1加权DCEPMRI的K_trans值及图,测量各个临床级别脑胶质瘤病灶面积差异。结果 低级别胶质瘤微血管通透性较低、肿瘤浸润范围小,T1加权DCEPMRI与常规增强MRI所测病灶面积误差达 0.2%~0.3%\[Ⅰ、Ⅱ级分别为2.93 cm²∶2.46 cm²(t=6.90,P=0.000)、4.18 cm²∶3.21 cm²(t=10.22,P=0.000)\];高级别胶质瘤微血管通透性较高、肿瘤浸润范围大,T1加权DCEPMRI与常规增强MRI所测量病灶面积误差达 25.1%~26.3%\[Ⅲ、Ⅳ级分别为6.46 cm²∶5.48 cm²(t=10.83,P=0.000)、8.26 cm²∶6.52 cm²(t=18.53,P=0.000)\]。结论 以T1加权DCEPMRI技术得到的微血管通透性相关定量参数K_trans值及彩图为胶质瘤放疗靶区确定提供了更为准确信息,可作为评价肿瘤体积新方法。     

Characterization of a human tumorsphere glioma orthotopic model using magnetic resonance imaging

Magnetic resonance imaging (MRI) is the imaging modality of choice by which to monitor patient gliomas and treatment effects, and has been applied to murine models of glioma. However, a major obstacle to the development of effective glioma therapeutics has been that widely used animal models of glioma have not accurately recapitulated the morphological heterogeneity and invasive nature of this very lethal human cancer. This deficiency is being alleviated somewhat as more representative models are being developed, but there is still a clear need for relevant yet practical models that are well-characterized in terms of their MRI features. Hence we sought to chronicle the MRI profile of a recently developed, comparatively straightforward human tumor stem cell (hTSC) derived glioma model in mice using conventional MRI methods. This model reproduces the salient features of gliomas in humans, including florid neoangiogenesis and aggressive invasion of normal brain. Accordingly, the variable, invasive morphology of hTSC gliomas visualized on MRI duplicated that seen in patients, and it differed considerably from the widely used U87 glioma model that does not invade normal brain. After several weeks of tumor growth the hTSC model exhibited an MRI contrast enhancing phenotype having variable intensity and an irregular shape, which mimicked the heterogeneous appearance observed with human glioma patients. The MRI findings reported here support the use of the hTSC glioma xenograft model combined with MRI, as a test platform for assessing candidate therapeutics for glioma, and for developing novel MR methods.