The developmental history of the gadolinium chelates as intravenous contrast media for magnetic resonance

The developmental history of the gadolinium chelates, which spans 30 years, is described, focusing, in part, on the seminal work with each of the major agents in use today. By examining this history, insight is gained into important issues of efficacy and safety, with valuable lessons to be learned from the mistakes made during this period. An overview of physicochemical characteristics and chemical structures is also provided. The review concludes with a discussion of current research directions involving this field, which is that of the intravenous contrast media for magnetic resonance, in the past 5 years.     

Observation of cerebrospinal fluid flow with echo-planar magnetic resonance imaging

Using echo-planar (EP) magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) flow patterns have been demonstrated in the normal subject and patients with pathological conditions including communicating hydrocephalus, aqueduct stenosis and syringohydromyelia. Snap-shot imaging times of 128 ms allow detailed demonstration of transient intraventricular CSF flow patterns, which is not possible with conventional MRI. The potential of EPI as a method for qualitative and quantitative assessment of CSF dynamics is illustrated.     

Metabolites in ventricular cerebrospinal fluid detected by proton magnetic resonance spectroscopic imaging

Normally, ventricular cerebrospinal fluid (CSF) contains low levels of all metabolite signals on proton magnetic resonance spectroscopic imaging (MRSI). We present here three cases (two with seizure disorders, one with a central nervous system lymphoma) who presented with unusually elevated CSF signals on MRSI. Based on chemical shifts and in vitro studies (in one case), the signals were assigned to propan-1,2-diol (PD), acetone, and lactate, respectively. These compounds were either exclusively, or more readily, detected in CSF than in brain. Proton MRSI conveniently screens both brain and CSF for abnormal metabolism simultaneously.     

The contribution of gadolinium to the magnetic resonance diagnosis of spondylodiscitis]

To determine the contribution of Gd-DTPA to the evaluation of vertebral infections 16 MR examinations with i.v. Gd-DTPA injection were performed on 12 patients with diagnosis of spondylodiscitis. All patients were examined with both SE T1- and SE T2-weighted sequences. The SE T1-weighted sequence was repeated following i.v. Gd-DTPA injection (0.1 nmol/kg). Signal intensities and visibility of the lesions were evaluated with MR. For each lesion the grade of visibility on SE T1-weighted sequence was compared with the grade of visibility on SE T2-weighted sequence. Moreover, for each study the information obtained by the combined evaluation of SE T1-weighted sequence without and with Gd-DTPA was compared with the information obtained by combined SE T1- and SE T2-weighted sequences. Gd-DTPA was useful in the evaluation of lesions of the discal space, showing in all cases an area of low signal intensity with peripheral enhancement; this finding allowed, in some cases, to differentiate mild spondylodiscitis from degenerative features. Gd-DTPA was also very useful in determining the extent of the disease: in comparison with MR study without contrast media, the combined evaluation of SE T1-weighted sequence without and with Gd-DTPA better showed the extent of the disease in 7/8 cases (88%).     

B-waves in cerebral and spinal cerebrospinal fluid pulsation measurement by magnetic resonance imaging

OBJECTIVE: Noninvasive measurement of B-waves is possible by magnetic resonance (MR) imaging using echo planar imaging (EPI) sequences. In this study, the proportion of B-waves in the cerebrospinal fluid (CSF) of the spinal canal and in the aqueductus cerebri was evaluated under normal and pathologic conditions, respectively. The proportion of the influence of pulse and respiration on the CSF pulsations was estimated. METHODS: The spinal CSF was evaluated in 7 volunteers at 5 spinal levels (C1, C2/3, C 6/7, T5, and T12). Examination of the CSF frequencies at the aqueduct was performed in 14 volunteers, 10 patients with normal pressure hydrocephalus, and 5 patients with an aqueductal stenosis. An EPI sequence was applied at 1.5 T. During the 8-minute measurement time, pulse and respiration were coregistered. A MATLAB routine analyzed the spectral portion of the B-waves and the pulse- and respiration-dependent frequencies of the CSF. RESULTS: The amount of B-waves was small in cerebral (2.5%) and spinal measurements (3.4%) but significantly higher in the spinal CSF (P < 0.001). There was no statistically different amount of B-waves in the aqueduct for volunteers and hydrocephalic patients and between the different spinal levels in healthy volunteers. Spinal measurements revealed a rising portion of respiration-related frequencies from C1 to T12, whereas the portion of pulse-related frequencies declined. CONCLUSIONS: The data support that B-waves are a physiologic phenomenon. They can be delineated in the spinal and cerebral CSF. A higher amount of spinal B-waves reflects a stronger venous and respiratory influence.     

磁共振3 D-Cube T2序列成像对脑脊液鼻漏的诊断价值

目的探讨磁共振3D-Cube T2序列成像在脑脊液鼻漏中的临床应用。方法回顾性分析2017年2月—2018年8月陆军军医大学第二附属医院收治的脑脊液鼻漏患者17例,其中10例为颅脑创伤,7例为垂体瘤术后。行MRI常规检查及3D-Cube T2序列成像,研究3D-Cube T2序列脑脊液鼻漏的表现,总结3D-Cube T2序列成像对脑脊液鼻漏诊断的优势。结果 17例患者发现脑脊液鼻漏14例,表现为鼻腔或鼻窦内与颅内脑脊液信号一致的高信号影,并可见沟通二者相连的线状高信号影。14例鼻漏患者一共发现漏口16个,分别位于右侧前组筛窦及上鼻道7个、额窦6个、蝶窦及鞍旁2个、筛板1个。结论磁共振3D-Cube T2序列为重T2加权水成像,脑脊液在此序列图像上表现为高信号,通过图像后处理能多角度展示脑脊液鼻漏漏口的确切位置。     

Intracranial oscillations of cerebrospinal fluid and blood flows: analysis with magnetic resonance imaging

PURPOSE: To detect oscillations of the cerebrospinal fluid (CSF) flow related to the heartbeat and frequencies lower than 0.6 Hz and to compare these oscillations of CSF and blood flow in cerebral vessels by using echo planar imaging in real time mode. The existence of such waves has been well known but has not yet been shown by MRI. MATERIALS AND METHODS: In a slice perpendicular to the aqueduct, CSF flow as well as CBF, could be determined in sagittal sinus, basilar artery, and capillary vessels. After Fourier analysis, four frequency bands were assigned. RESULTS: In the very high-frequency (heart rate) range, the integrals under the CSF curves were more closely related to arterial CBF than to changes in the sinus. Also, in the high-frequency (respiration rate), low-frequency (0.05-0.15 Hz), and very-low-frequency (0.008-0.05 Hz) ranges, the integrals under the CSF curves corresponded with arterial and capillary CBF. CONCLUSION: Slow and fast oscillations in CSF flow are detectable in healthy persons with a proportional allotment to arterial and capillary CBF.     

Diffusion-weighted magnetic resonance imaging of cerebrospinal fluid in patients with and without communicating hydrocephalus

Background: Recent concepts about cerebrospinal fluid (CSF) circulation in communicating hydrocephalus (CoHy), which is also termed “restricted arterial pulsation hydrocephalus,” suggest reduced arterial pulsations of subarachnoid vessels with a smaller amount of CSF shifted in subarachnoid spaces during the early systole. The postulated restriction of subarachnoid arterial pulsations in CoHy should induce a smaller motion artifact and reduced local stream effects in CSF in magnetic resonance (MR) diffusion-weighted imaging (DWI).

Purpose: To investigate the maximum diffusivity in CSF in patients with and without CoHy using DWI.

Material and Methods: 12 patients without CSF circulation disturbances and six cases with proven CoHy were assessed. Diffusion was measured in six noncollinear directions without triggering the arterial pulse wave (scan time 6:45 min, voxel size 2×2×2 mm). Due to expected artifacts, the calculated maximum diffusivity was called apparent diffusivity. Regional high and low apparent diffusivity was assessed in CSF spaces on newly created 3D CSF motion maps.

Results: Patients with regular CSF circulation exhibited high apparent diffusivity in CSF in basal subarachnoid spaces, whereas apparent diffusivity was low there in patients with CoHy.

Conclusion: DWI opens a feasible approach to study CSF motion in the neurocranium. Restricted arterial pulsations seem to be involved in CoHy.     

Extensive cerebrospinal fluid enhancement following gadolinium chelate administration: possible pathogenesis

Diffuse cerebrospinal fluid (CSF) enhancement following gadolinium administration is a rarely recognized phenomenon, and its mechanism is not fully understood. We report two cases of diffuse CSF enhancement following gadolinium administration and review the literature. We conclude that the contributing factors of this phenomenon include blood-CSF barrier disruption, increased dosage, impair renal clearance, delayed imaging after contrast administration, and use of different pulse sequences.     

静脉注射钆类对比剂对乳腺正常腺体及肿瘤组织MR扩散加权成像的影响

目的 探讨乳腺MR DWI质量及正常腺体与癌组织的ADC值是否受到钆类对比剂增强扫描的影响.方法 对25例已经针吸穿刺或粗针活检病理证实为乳腺癌的患者在静脉注射Gd-DTPA前、后行DWI扣描,将R01分别置于癌灶及正常腺体,应用配对t检验及非参数检验比较b值=0及1000 s/mm2时增强前后图像中癌灶和正常腺体的信噪比(SNR)、对比噪声比(CNR)及ADC值的变化.结果 增强前、后癌灶的SNR(34.56±11.34和33.60±14.34)与正常腺体的SNR(9.88±3.16和10.42±4.18)以及图像CNR(24.16±9.05和22.26±10.05)的差异无统计学意义(P癌灶SNR=0.70,P正常腺体SNR=0.11;PCNR=0.17);增强前后癌灶的ADC值分别为(0.96±0.13)×10-3和(0.95±0.14)×10-3mm2/s,正常腺体分别为(1.90±0.47)×10-3 和(1.91±0.61)×10-3mm2/s,两者在增强后ADC值与其增强前差异均无统计学意义(P=0.20和0.97).结论 乳腺痛组织和正常腺体DWI的质量及ADC测量值不会受到Gd-DTPA的影响,故在乳腺MR扫描中,DWI可以在增强扫描后进行.     

Detection of cerebrospinal fluid leakage: initial experience with three-dimensional fast spin-echo magnetic resonance myelography

Background: The pathogenesis of cerebrospinal fluid (CSF) hypovolemia is supposed to be caused by CSF leakage through small dural defects.

Purpose: To compare source three-dimensional (3D) fast spin-echo (FSE) images of magnetic resonance (MR) myelography with radionuclide cisternography findings, and to evaluate the feasibility of MR myelography in the detection of CSF leakage.

Material and Methods: A total of 67 patients who were clinically suspected of CSF hypovolemia underwent indium-111 radionuclide cisternography, and 27 of those who had direct findings of CSF leakage were selected for evaluation. MR myelography with 3D FSE sequences (TR/TE 6000/203 ms) was performed at the lumbar spine for all patients. We evaluated source images and maximum intensity projection (MIP) images of MR myelography, and the findings were correlated with radionuclide cisternography findings. MR myelography of five healthy volunteers was used as a reference. The MR visibility of the CSF leakage was graded as definite (leakage clearly visible), possible (leakage poorly seen), or absent (not shown).

Results: CSF leakage was identified with source 3D FSE images in 22 (81.5%) of 27 patients. Of the 22 patients, 16 were graded as definite and six were graded as possible. For the definite cases, 3D FSE images clearly showed the extent of the leaked CSF in the paraspinal structures. In the remaining five patients with absent findings, radionuclide cisternography showed only slight radionuclide activity out of the arachnoid space.

Conclusion: Source 3D FSE images of MR myelography seem useful in the detection of CSF leakage. Invasive radionuclide cisternography may be reserved for equivocal cases only.     

Cerebrospinal fluid dynamics and relation with blood flow: a magnetic resonance study with semiautomated cerebrospinal fluid segmentation

RATIONALE AND OBJECTIVES: To investigate and measure temporal and amplitude aspects of blood and cerebrospinal fluid (CSF) flow waveform relations. METHODS: A cine phase-contrast magnetic resonance imaging pulse sequence was used to measure blood and CSF flow in 16 healthy subjects aged 27 +/- 4 years. A semiautomated segmentation algorithm was developed to study CSF flow. RESULTS: Standard deviations of the aqueductal and cervical flow measurements carried out by five observers were 1% and 4%, respectively. The peak systolic arterial flow was 1087 +/- 169 mL/min, and the peak cervical CSF flush (173 +/- 59 mL/min) occurred at 5% +/- 3% of the cardiac cycle after the internal carotid systolic peak flow. Peak aqueductal flush flow (13 +/- 5 mL/min) occurred at 21% +/- 7% of the cardiac cycle after the internal carotid systolic peak flow. CONCLUSIONS: The CSF segmentation algorithm is reproducible. Brain expansion was quickly regulated by a major extracerebral CSF flush flow, whereas ventricular CSF made only a very small contribution.     

Brain magnetic resonance with magnetization transfer in multiple sclerosis. Lesion hyperintensity before and after intravenous gadolinium administration

PURPOSE: The possibility of detecting contrast agent extravasation (i.e., active hemorrhage) with dynamic conventional Computed Tomography (CT) in patients with abdominal trauma has already been reported in small series. We report our experience in the demonstration of contrast material extravasation using helical CT; we also investigate the diagnostic and clinical value of this finding. MATERIAL AND METHODS: January 1997 to July 1998, we examined 41 consecutive patients with upper abdominal trauma. Twelve patients (29%) had contrast material extravasation. The examinations were performed with a helical unit and volumetric acquisitions (thickness 8-10 mm, pitch 1, reconstruction interval 5-8 mm). The intravenous contrast medium (350 mgI/mL, 130-140 mL) was administered with rapid infusion (2-2.5 mL/s, 40-50 s acquisition delay from bolus starting) and using a power injector. We reviewed the CT studies and clinical records of these 12 patients. Contrast agent extravasation was considered present when this finding, not recognizable on plain scans, showed equal attenuation to or higher attenuation than the vessels within the same level. Moreover we assessed leak site, CT appearance, the direct visualization of the involved vessel, the evidence of other abdominal or extra-abdominal injuries, the CT signs of hypovolemic shock, clinical and surgical data. For comparison, we finally evaluated 50 examinations performed with a conventional CT scanner in subjects with abdominal trauma. RESULTS: Active hemorrhage involved the abdominal wall in 1 case (intercostal artery), the solid organs in 4 (splenic in 2, hepatic in 1, of the middle hepatic vein in 1), the peritoneal cavity in 3 (splenic, midcolic, and gastroduodenal artery in 1 each), the retroperitoneum in 4 (renal pedicle in 2, renal parenchyma in 1, lumbar artery in 1). In all cases the site of contrast extravasation corresponded at surgery to the site of active bleeding. The pattern was localized in 10 cases and diffuse in 2. The involved vessel could be identified in 5 cases while in the other ones the origin could be inferred from the leakage site. Associated injuries of upper abdominal organs were seen in 11 of 12 patients and extra-abdominal trauma in 6. In 4 cases there were CT features of hypovolemia. One patient died during transport to the operating room and another after surgery, while all the others survived. Contrast extravasation was identified in 9 (18%) of the patients examined with a conventional CT unit. CONCLUSIONS: Active contrast material extravasation can be recognized with conventional CT scanners, though it has been considered a rare finding. Helical CT seems to increase the detection rate and especially to boost the radiologist's confidence in this diagnosis. Though active bleeding is identified in severely-injured subjects requiring urgent intervention and may be associated with findings of hypovolemic shock, it should not be considered itself as a negative prognostic factor. Contrast extravasation is due to ongoing hemorrhage and its detection is critical for urgent treatment. Accurate anatomical location permits to choose surgical management or transcatheter embolization and thus decreases time consumption for precise bleeding site identification.     

心脏磁共振延迟强化技术进展

心脏磁共振（CMR）延迟强化是诊断心肌梗死、心肌病及评估病变范围最重要的检查技术。目前临床应用的单次激发相位敏感反转恢复（SS-PSIR）序列、自由呼吸运动伪影校正PSIR（MOCO-PSIR）序列和非血流依赖黑血延迟强化（FIDDLE）序列,相比常规采用的PSIR序列能够实现呼吸、心脏运动伪影及血池信号抑制,可明显改善影像质量,有利于更好地指导治疗并进行预后评价。就多种CMR延迟强化技术原理及应用作一综述。     

High-dose applications of gadolinium chelates in magnetic resonance imaging.

Administration of gadolinium chelates at doses greater than 0.1 mmol/kg IV can potentially improve both lesion detection and the assessment of tissue perfusion. Preliminary results are presented in clinical patients and two animal models. In human intracranial metastatic disease, administration of 0.3 (cumulative dose) mmol/kg gadoteridol (Gd HP-DO3A) has permitted detection of additional lesions not visualized at 0.1 mmol/kg. In a rabbit model of focal liver disease, 0.5 mmol/kg IV provided superior enhancement of both normal parenchyma and lesion rim compared to doses of 0.25 and 0.1. Dynamic imaging (T1-weighted turbo-FLASH) immediately following bolus injection of 0.5 mmol/kg permitted direct visualization (on unsubtracted images) of an acute perfusion defect in the cat brain not visible on conventional T1- and T2-weighted scans.     

心脏MRI在扩张型心肌病中的应用价值

目的 探讨1.5T心脏磁共振成像(CMRI)在扩张型心肌病(DCM)中的应用价值.方法 选取DCM患者45例及健康对照者25例,均进行CMRI检查,通过LGE序列判断左心室有无心肌纤维化将DCM组患者分为LGE(+)组和LGE(-)组,测如下结构及功能参数:LVEDD、LVESD、LVEDV、LVESV、LVEF、LV...     

Nanotemplate-engineered nanoparticles containing gadolinium for magnetic resonance imaging of tumors

PURPOSE: To design nanoparticles containing accessible gadolinium atoms (Gd-NPs) as a contrast agent for magnetic resonance imaging of tumors. METHODS: Nanoparticles containing phospholipid-chelates (phosphoethanolamine diethylenetriaminepentaacetate) and DSPE-PEG (MW5000) were prepared from Brij 78 and stearyl alcohol using the nanotemplate engineering approach. After addition of GdCl3, the presence of gadolinium on the surface of nanoparticles was quantified using inductively coupled plasma atomic emission spectroscopy. The in vitro relaxivities of the Gd-NPs in phosphate buffered saline were assessed at 4.7 T. The conditional binding constants of nanoparticle formulations were determined spectrophotometrically by competitive titration. Transmetallation kinetics of Gd from nanoparticles with Cu2+ and Zn2+ as the competing ions was measured in acetate buffer. The biodistribution profiles, pharmacokinetics, and contrast enhancement in tumor region was studied after administration of Gd-NPs to nude mice bearing A549 lung carcinoma xenografts. RESULTS: Gd-NPs with an average diameter of 138 nm possessing surface chelating functions were prepared from GRAS (generally regarded as safe) materials. The longitudinal relaxivity (r1) and transverse relaxivity (r2) of Gd-NPs in 10% fetal bovine serum at 4.7 T were 7.1 (+/-0.2) and 13.0 (+/-0.7) 1/mM/s, respectively. These pegylated Gd-NPs had enhanced relaxivities and exhibited particle size stability, sufficient binding affinity, and kinetic inertness under physiologic conditions. The contrast enhancement in tumors was demonstrated 40, 120, and 360 minutes after intravenous injection of Gd-NPs at a dose of 0.1 mmol Gd/kg. The Gd plasma concentration of Gd-NPs over a period of 24 hours fit a two-compartmental model with Cl sys = 0.89 mL/h and MRT = 5.93 h. The amount of Gd that accumulated in the tumor region was consistent with the estimated value obtained by T1 measurements using MR imaging. CONCLUSION: Pegylated nanoparticles composed of biocompatible, biodegradable materials and possessing accessible Gd ions on their surface induce relaxivities in the bulk water signal and accumulated sufficiently in tumors, demonstrating their utility as potential magnetic resonance imaging tumor contrast enhancement agents.     

Effect of the rate of gadolinium injection on magnetic resonance pulmonary perfusion imaging.

PURPOSE: To determine whether the injection rate of contrast agent affects the dynamics of enhancement of the pulmonary parenchyma on magnetic resonance (MR) pulmonary perfusion imaging. MATERIALS AND METHODS: Fifteen healthy volunteers underwent enhanced MR pulmonary perfusion imaging to evaluate the effects of different injection rates. Injection rates were 1, 3, or 5 mL/second. Regions of interest (ROIs) were chosen in the lung and aorta to analyze the change in signal intensity over time. RESULTS: As the injection rate increased, the peak enhancement occurred significantly earlier (P = 0.0012), but the peak enhancement signal-to-noise ratio (SNR) value was not affected (P = 0.25). With the 3- and 5-mL/second injection rates, images of both the pulmonary circulation and systemic circulation were obtained separately. However, with 1 mL/second, higher enhancement of the aorta was overlapped with peak enhancement of the lung tissue. CONCLUSION: The injection rate affects the enhancement profiles of the pulmonary parenchyma.