Diffusion tensor imaging and tractography for preoperative assessment of benign peripheral nerve sheath tumors.
- 作者列表："Gersing AS","Cervantes B","Knebel C","Schwaiger BJ","Kirschke JS","Weidlich D","Claudi C","Peeters JM","Pfeiffer D","Rummeny EJ","Karampinos DC","Woertler K
PURPOSE:To evaluate the diagnostic value of fiber tractography and diffusivity analysis generated from 3D diffusion-weighted (DW) sequences for preoperative assessment of benign peripheral nerve sheath tumors. METHOD:MR imaging at 3 T was performed in 22 patients (mean age 41.9 ± 17.1y, 13 women) with histologically confirmed schwannomas (N = 18) and histologically confirmed neurofibromas (N = 11), including a 3D DW turbo spin echo sequence with fat suppression. Diffusion tensor parameters were computed and fiber tracks were determined. Evaluation was performed by two radiologists and one orthopedic surgeon blinded for final diagnosis. Mean diffusivity was computed to allow further assessment of tumor microstructure. Preoperative fascicle visualization was graded, fascicles were categorized regarding anatomical location and amount of fascicles surrounding the tumor. The agreement of imaging findings with intraoperative findings was assessed. RESULTS:On 78.3 % of the DTI images, the fascicle visualization was rated as good or very good. Tractography differences were observed in schwannomas and neurofibromas, showing schwannomas to be significantly more often located eccentrically to the nerve (94.8 %) than neurofibromas (0 %, P < 0.01). Fascicles were significantly more often continuous (87.5 %) in schwannomas, while in neurofibromas, none of the tracks was graded to be continuous (0 %, P = 0.014). A substantial agreement between fiber tracking and surgical anatomy was found regarding the fascicle courses surrounding the tumor (κ = 0.78). Mean diffusivity of schwannomas (1.5 ± 0.2 × 10-3 mm2/s) was significantly lower than in neurofibromas (1.8 ± 0.2 × 10-3 mm2/s; P < 0.001). The Youden index showed an optimal cutoff at 1.7 × 10-3 mm2/s (sensitivity, 0.91; specificity, 0.78; J = 0.69). CONCLUSIONS:Preoperative diffusion tensor imaging allowed to accurately differentiate between schwannomas and neurofibromas and to describe their location in relation to the nerve fascicles for preoperative planning.
目的: 评价纤维纤维束成像和三维弥散加权 (DW) 序列产生的扩散系数分析对良性周围神经鞘瘤术前评估的诊断价值。 方法: 对 22 例患者 (平均年龄 41.9 ± 17 岁) 进行 3 t MR 成像。1y，13 例女性)，组织学证实为神经鞘瘤 (n = 18)，组织学证实为神经纤维瘤 (n = 11)，包括具有脂肪抑制的 3D DW turbo 自旋回波序列。计算扩散张量参数并确定纤维轨迹。由 2 名放射科医生和 1 名矫形外科医生盲法进行评估以获得最终诊断。计算平均扩散系数，以便进一步评估肿瘤微结构。术前成束可视化进行分级，根据解剖位置和肿瘤周围成束的数量对成束进行分类。评估影像学检查结果与术中检查结果的一致性。 结果: 在 78.3% 的 DTI 图像上，分册可视化评分为良好或非常好。在神经鞘瘤和神经纤维瘤中观察到纤维束造影差异，显示神经鞘瘤明显更常见于神经 (94.8%) 而非神经纤维瘤 (0%，p <0.01)。在神经鞘瘤中，束束更经常连续 (87.5%)，而在神经纤维瘤中，没有一个束被分级为连续 (0%，p = 0.014)。关于肿瘤周围的分册路线，发现纤维追踪和手术解剖之间有实质性的一致性 (κ = 0.78)。神经鞘瘤的平均扩散率 (1.5 ± 0.2 × 10-3 mm2/s) 明显低于神经纤维瘤 (1.8 ± 0.2 × 10-3 mm2/s); P <0.001)。Youden 指数显示最佳截断值为 1.7 × 10-3 mm2/s (灵敏度，0.91; 特异度，0.78; J = 0.69)。 结论: 术前弥散张量成像能够准确区分神经鞘瘤和神经纤维瘤，并描述它们与神经束的位置，用于术前规划。
METHODS:PURPOSE:To generate a preclinical model of isocitrate dehydrogenase (IDH) mutant gliomas from glioma patients and design a MRS method to test the compatibility of 2-hydroxyglutarate (2HG) production between the preclinical model and patients. METHODS:Five patient-derived xenograft (PDX) mice were generated from two glioma patients with IDH1 R132H mutation. A PRESS sequence was tailored at 9.4 T, with computer simulation and phantom analyses, for improving 2HG detection in mice. 2HG and other metabolites in the PDX mice were measured using the optimized MRS at 9.4 T and compared with 3 T MRS measurements of the metabolites in the parental-tumor patients. Spectral fitting was performed with LCModel using in-house basis spectra. Metabolite levels were quantified with reference to water. RESULTS:The PRESS TE was optimized to be 96 ms, at which the 2HG 2.25 ppm signal was narrow and inverted, thereby leading to unequivocal separation of the 2HG resonance from adjacent signals from other metabolites. The optimized MRS provided precise detection of 2HG in mice compared to short-TE MRS at 9.4 T. The 2HG estimates in PDX mice were in excellent agreement with the 2HG measurements in the patients. CONCLUSION:The similarity of 2HG production between PDX models and parental-tumor patients indicates that PDX tumors retain the parental IDH metabolic fingerprint and can serve as a preclinical model for improving our understanding of the IDH-mutation associated metabolic reprogramming.
METHODS:BACKGROUND:Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population. METHODS:Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients' age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test. RESULTS:181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006). CONCLUSIONS:The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.
METHODS:BACKGROUND:Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. Tumor recurrence occurs in virtually all cases, therefore, despite any treatment, the median survival is very low (14.6 months), which makes the approach to these patients a challenging clinical issue. MAIN BODY:The escalating costs and times required for new medications to reach the bedside make repurposing or repositioning of old drugs, when scientific bases allow their use in other pathologies, an appealing strategy. Here, we analyze a number of literature data concerning the antipsychotic chlorpromazine, the founder of the phenothiazines class of drugs, a medication widely used in the clinics for approximately 60 years. The drug exerts its effects on psychiatric patients by interfering with the dopamine receptor D2, although more recent pharmacodynamics studies ascribe chlorpromazine a series of biological effects on cancer cells, all converging in hindering also glioblastoma survival capabilities. SHORT CONCLUSIONS:On these bases, and assisted by the information on the well-established chlorpromazine toxicity and dosage in humans, we designed a Phase II clinical trial involving the combination of chlorpromazine with the standard treatment, temozolomide, in the adjuvant phase of the therapeutic protocol. Patients displaying hypo-methylation of the MGMT gene, and thus intrinsically resistant to temozolomide, will be enrolled. The endpoints of this study are the analysis of toxicity and clinical activity, as evaluated in terms of Progression-Free Survival, of the association of chlorpromazine with the first-line treatment for this very serious form of cancer.