Quantitative assessment of central nervous system disorder induced by prenatal X-ray exposure using diffusion and manganese-enhanced MRI

Prenatal radiation exposure induces various central nervous system (CNS) disorders depending on the dose, affected region and gestation period. The goal of this study was to assess noninvasively a CNS development disorder induced by prenatal X-ray exposure using quantitative manganese-enhanced MRI (MEMRI) as well as apparent diffusion coefficient (ADC) and transverse relaxation time (T(2)) maps in comparison with immunohistological staining. The changes in ΔR(1) (increase in the longitudinal relaxation rate (R(1)) from before and after MnCl(2) administration.) induced by the Mn(2+) contrast agent were evaluated in the CNS of normal and prenatally irradiated rats. ADC and T(2) were also compared with the histological results obtained using hematoxylin and eosin (to estimate cell density), activated caspase-3 (apoptotic cells) and glial fibrillary acidic protein (proliferation of astrocytes/astroglia). We found the following: (i) the decreased Mn(2+) uptake (indicated by a smaller ΔR(1)) for radiation-exposed rats was predominantly correlated with a decrease in cell viability (apoptotic cytopathogenicity) and CNS cell density after prenatal radiation exposure; (ii) the longer T(2) and ADC were associated with a decrease in CNS cell density and apoptotic alteration after radiation exposure. In addition to the slight proliferation of astroglia (+58%), there was a substantial decrease in cell density (-78%) and an excessive increase in apoptotic cells (+613%) in our prenatal radiation exposure model. The results suggest that MEMRI in the prenatal X-ray exposure model predominantly reflected the decrease in cell density and viability rather than the proliferation of astroglia. In conclusion, quantitative MEMRI with ADC/T(2) mapping provides objective information for the in vivo assessment of cellular level alterations by prenatal radiation exposure, and has the potential to be used as a standard approach for the evaluation of the cellular damage of radiotherapy.     

Assessment of the dentin-pulp complex response to caries by ADC mapping

The prognostic potential of apparent diffusion coefficient (ADC) mapping was studied as complemented by high-resolution 3D T(1)-weighted MRI in the assessment of dentin-pulp complex response to caries. Twenty-six extracted human teeth, with or without caries lesions of different grades in accord with the International Caries Detection and Assessment System (ICDAS), were analyzed by high-resolution MRI at 2.35 T. A signal rise in demineralized hard dental tissues in high-resolution T(1)-weighted MR images enabled assessment of the demineralization depth over the whole range of ICDAS scores. ADC maps of the teeth were calculated from corresponding diffusion-weighted images of four different b values: 0, 132, 317, 635 s/mm(2). These maps enabled reliable differentiation between intact (ADC > 1.0·10(-9) m(2)/s) and affected (ADC < 1.0·10(-9) m(2)/s) regions of dental pulp. Linear regression analyses of demineralization depth in relation to ICDAS score and then also to average ADC of dental pulp showed that a demineralization depth increase of one millimeter corresponds to an ICDAS score increase of 1.2 and an average ADC decrease of 0.07·10(-9) m(2)/s. Results of the study indicate that the average ADC value of dental pulp could be used as a potential marker to assess tissue response to caries comparable to that of ICDAS scoring.     

Characterisation of in vivo ovarian cancer models by quantitative 1H magnetic resonance spectroscopy and diffusion-weighted imaging

Magnetic resonance imaging (MRI) and spectroscopy (MRS) offer powerful approaches for detecting physiological and metabolic alterations in malignancies and help investigate underlying molecular mechanisms. Research on epithelial ovarian carcinoma (EOC), the gynaecological malignancy with the highest death rate characterised by frequent relapse and onset of drug resistance, could benefit from application of these molecular imaging approaches. In this study, MRI/MRS were used to characterise solid tumour models obtained by subcutaneous (s.c.) or intraperitoneal (i.p.) implantation of human SKOV3.ip cells in severe combined immunodeficiency (SCID) mice. In vivo MRI/MRS, ex vivo magic-angle-spinning (MAS), and in vitro (1)H-NMR measurements were carried out at 4.7 T, 9.4 T, and 9.4/16.5 T, respectively. MRI evaluation was performed by T1-, T2-, and diffusion-weighted (DW) multislice spin-echo imaging. The in vivo (1)H spectra of all tumour models showed a prominent resonance of total choline-containing metabolites (tCho). Quantitative in vivo MRS of both i.p. and s.c. SKOV3.ip xenografts showed that the mean tCho content was in the 2.9-4.5 mM range, with a mean PCho/tCho ratio of 0.99 ± 0.01 [23 examinations, 14-34 days post injection (dpi)], in good agreement with ex vivo and in vitro analyses. Myo-inositol ranged between 11.7 and 17.0 mM, with a trend towards higher values in i.p. xenografts at 14-16 dpi. The average apparent diffusion coefficient (ADC) values of SKOV3.ip xenografts [1.64 ± 0.11 (n = 9, i.p.) and 1.58 ± 0.03 x10(-3) mm(2)/s (n = 7, s.c.)] were in agreement with values reported for tumours from patients with EOC, while the mean vascular signal fraction (VSF) was lower (≤ 4%), probably due to the more rapid growth of preclinical models. Both s.c. and i.p. xenografts are valuable preclinical models for monitoring biochemical and physiopathological changes associated with in vivo EOC tumour growth and response to therapy, which may serve as the basis for further clinical development of noninvasive MR approaches.     

弥散加权成像在不同病理类型的脑膜瘤鉴别中的应用

目的:探索弥散加权成像中定量ADC在鉴别诊断不同病理亚型良、恶性脑膜瘤中的价值.方法:研究对象共141例,男女比例为1:2.7;均为手术病理证实.扫描仪为CE 1.5T.弥散加权扫描b值为1000s/mm<'2>.rADC为病灶实质部分ADC比对侧正常白质ADC.结果:t检验良性脑膜瘤和恶性脑膜瘤rADC两组数据有明显统计学差异(P<0.01).血管瘤型脑膜瘤的实质rADC都要比其他病理亚型高(P<0.01),间变型脑膜瘤rADC比纤维型、上皮型、血管瘤型低(P<0.05).而纤维型、上皮型和非典型脑膜瘤之间rADC没有统计学差异(P>0.05).间变型脑膜瘤瘤周水肿rADC大于纤维型脑膜瘤(P<0.05).其他病理亚型脑膜瘤瘤周水肿rADC无统计学差异(P>0.05).结论:肿瘤实质rADC可以在鉴别良性和恶性脑膜瘤以及不同病理亚型脑膜瘤中发挥重要作用,瘤周水肿rADC在鉴别间变型脑膜瘤有重要意义.DWI对脑膜瘤术前评价有较高的实践价值.     

基于MRI T2WI图像的游程矩阵纹理分析联合ADC值对前列腺癌分化程度的评估

目的探究MRI T2WI图像游程矩阵纹理分析技术联合ADC值在评估前列腺癌分化程度应用中的可行性,以期术前量化评估前列腺癌的分化程度。方法回顾性分析50例经手术病理证实的前列腺癌患者MRI影像资料,并依据Gleason评分将≤6分归为高分化组(25例);将>6分归为低分化组(25例)。对前列腺进行标准化分区,依据病理结果分别选取病变T2WI横断位图像最大层面,采用Mazda纹理分析软件勾画感兴趣区并进行游程矩阵纹理分析,并在DWI图像选取相应感兴趣区测定ADC值,对高、低分化两组前列腺癌进行数据统计分析。建立ROC曲线并计算联合预测因子进行诊断效能比较分析,对纹理参数及ADC值与分化程度之间的相关性进行检测。结果采用游程矩阵提取的5类参数中,水平方向(Horzl-GLNU)、垂直方向(Vertl-GLNU)、45度方向(45dgr-GLNU)、135度方向(135dgr-GLNU)上的灰度不均匀性(GLNU)在高、低分化两组间有显著差异(P值均<0.05)。ADC值在不同分化程度之间有显著差异(P<0.05)。Horzl-GLNU、Vertl-GLNU、45dgr-GLNU、135dgr-GLNU与分化程度呈负相关(r值分别为-0.450、-0.442、-0.470、-0.464,P值均<0.05)。ADC值与分化程度呈正相关(r值为0.423,P值<0.05)。纹理参数中,45dgr-GLNU的ROC曲线下面积(AUC)最大(0.771),敏感性和特异性分别为56.0%、92.0%。ADC值的AUC值为0.837,敏感性和特异性分别为64.0%、76.0%。联合预测因子AUC值为0.869,敏感性和特异性分别为72.0%、88.0%,诊断效能得到提升。结论基于MRI T2WI图像的游程矩阵纹理分析联合ADC值可提高对术前前列腺癌分化程度的评估效能。     

Comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate,in cynomolgus monkeys

1. Trastuzumab deruxtecan (DS-8201a) is an antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) conjugated to a topoisomerase I inhibitor (DXd) at a drug-to-antibody ratio (DAR) of 7-8. Here, we examined the pharmacokinetic (PK) profiles of DS-8201a and DXd in cynomolgus monkeys, a cross-reactive species.

2. Following intravenous (iv) administration of DS-8201a, the linker was stable in plasma, and systemic DXd exposure was low. DXd was rapidly cleared following iv dosing. Biodistribution studies revealed that intact DS-8201a was present mostly in the blood without tissue-specific retention. The major pathway of excretion for DXd was the faecal route following iv administration of radiolabelled DS-8201a. The only detectable metabolite in the urine and faeces was unmetabolized DXd. DXd is a substrate of organic anion transporting polypeptides, P-gp, and breast cancer resistance protein.

3. In conclusion, the stable linker in circulation and the high clearance of DXd upon release resulted in the low systemic exposure to DXd. Furthermore, the minimal tissue-specific retention and rapid excretion of DXd into faeces as its unmetabolized form with potentially limited impact on drug???drug interaction as a victim were also critical elements of the PK profile of DS-8201a.