More than meets the eye: significant regional heterogeneity in human cortical T1

Segmented k-space acquisition of data was used to decrease the acquisition time and to increase the imaging resolution of the precise and accurate inversion recovery (PAIR) method of measuring T(1). We validated the new TurboPAIR method by measuring T(1) in 158 regions of interest in 12 volunteers, using both PAIR and TurboPAIR. We found a 3% difference between methods, which could be corrected by linear regression. After validation, the TurboPAIR method was used to test a hypothesis that there is significant regional heterogeneity in cortical T(1). We measured cortical gray matter T(1) in 11 right-handed volunteers, in 48 regions of interest scattered over frontal and parietal cortex, and in 46 ROIs along the central sulcus (CS). We found that T(1) in the CS is less than T(1) elsewhere in the cortex (p<0.001), and that there is considerable hemispheric asymmetry in T(1) in gray matter, but not in white matter. In central gray structures (caudate, thalamus, nucleus pulvinarus), and in the posterior CS (sensory cortex), right hemisphere T(1) was significantly greater than left hemisphere T(1) (p< or =0.004). In cortical gray matter of the frontal lobe and anterior CS (motor cortex), left hemisphere T(1) was significantly greater than right hemisphere T(1) (p< or =0.003). These findings demonstrate that there is considerable regional heterogeneity in human cortical T(1) that is unexplained by differences in tissue iron content, but may be evidence of an inherent anatomic asymmetry of the brain.     

Assessment of T1 time course changes and tissue-blood ratios after Gd-DTPA administration in brain tumors

Sequential T1 changes in brain tumor tissue after Gd-DTPA administration were investigated in 10 patients, including 4 meningiomas, 2 gliomas, 3 metastatic cerebral tumors and 1 brain abscess. T1 values were measured serially for 60 minutes following Gd-DTPA injection using a magnetic focusing technique. In vitro T1 of the whole blood samples was also comparatively examined. Time processes in the tissue-blood ratio (TBR) were calculated from two-point relaxation rates at 5 and 30 minutes. The obtained ratios of TBR were ranged from 1.0 to 3.0, probably depending on histological types of brain tumor (the value of 1.0 to 1.5 for meningioma and 1.5 to 3.0 for glioma and metastatic tumor). No significant changes in the T1 value were observed in the examined normal tissue and peritumoral edema. These results indicate that Gd-DTPA plays an important role not only as an image enhancer for tumor tissue but also as an indicator for estimating the blood-brain barrier function.     

Magnetic resonance spectroscopic imaging for visualization and correction of distortions in MRI: high precision applications in neurosurgery

We present a method for the quantification and correction of geometrical/intensity distortions of magnetic resonance images predominantly caused by bulk magnetic susceptibility shifts due to susceptibility heterogeneities of measured biologic tissues and shape of the object under investigation. The method includes precise and fast measurements of the static magnetic-field distribution inside the measured object and automated data processing. Magnetic-field deviations in the range −2.4; 2.6 ppm were found in the human brain at B₀ = 1.5 T. For routinely used imaging parameters, with a read gradient strength of about 1 mT/m, the magnetic-field perturbations in the human brain can cause geometrical distortions up to ±4 mm and intensity changes up to ±50%. MR images corrected by the described method are suitable for planning high precision applications in neurosurgery.     

Magnetic resonance of brain tumors: considerations of imaging contrast on the basis of relaxation measurements

Proton spin-lattice and spin-spin relaxation times have been measured in surgically-removed normal CNS tissues and a variety of tumors of the brain. All measurements were made at 20 MHz and 37 degrees C. Between grey and white matter from autopsy human or canine specimens significant differences in T1 or T2 were observed, with greater differences seen in T1. Such discrimination was reduced in samples obtained from live brain-tumor patients due to lengthening in T1 and T2 of white matter near tumorous lesions. Edematous white matter showed T1 and T2 values higher than those of autopsy disease-free white matter. Compared to normal CNS tissues, most brain tumors examined in this study demonstrated elevated T1 and T2 values. Exceptions, however, did exist. No definitive correlation was indicated on a T1 or T2 basis which allowed a distinction to be made between benign and malignant states. Furthermore, considerable variation in relaxation times occurred from tumor to tumor of the same type, suggesting that within a tumor type there are important differences in physiology, biology, and/or pathologic state. Such variation caused partial overlap in relaxation times among certain tumor types and hence may limit the capability of magnetic resonance imaging (MR) alone for the diagnosis of specific disease. Nonetheless, this study predicts that on the basis of T1 or T2 differences most brain tumors are readily detectable by MR via saturation recovery or inversion recovery with appropriate selections of pulse-spacing parameters. In general, tumors can be discriminated against white matter better than grey matter and contrast between glioma and grey matter is usually superior to that between meningioma and grey matter. This work did not consider tissue-associated proton density which should be addressed together with T1 and T2 for a complete treatment of MR contrast.     

Neurotoxicity of gadolinium contrast agents for magnetic resonance imaging in rats with osmotically disrupted blood-brain barrier

The neurotoxicity of intravenously injected Gadolinium (Gd) complexes to rats with disrupted blood-brain barrier (BBB) was evaluated. After disruption of the BBB by infusion of mannitol solution, one of several contrast agents tested was injected intravenously at a dose of 1 or 3 mmol Gd/kg, and neurological symptoms were graded. The concentrations of Gd in brain and plasma were also measured. Injection of Gd-DTPA at a dose of 3 mmol Gd/kg did not change behavior. On the other hand, Gd-DTPA-BMA, Gd-DO3A-butrol, and Gd-DO3A-HP each induced behavioral impairments, and some animals died within 1 h after injection. Gd-DO3A-HP showed lethal effect even at a dose of 1 mmol/kg. The concentration of Gd in the brain of the animals injected with Gd-DO3A-HP at 3 mmol Gd/kg was essentially the same as that of animals injected with Gd-DTPA at the same dose. The neurotoxicity of the contrast agents tested was graded as follows: Gd-DTPA ≤ Gd-DTPA-BMA = Gd-DO3A-butrol < Gd-DO3A-HP.     

MRI texture analysis on texture test objects, normal brain and intracranial tumors

Texture analysis was performed in three different MRI units on T1 and T2-weighted MR images from 10 healthy volunteers and 63 patients with histologically confirmed intracranial tumors. The goal of this study was a multicenter evaluation of the usefulness of this quantitative approach for the characterization of healthy and pathologic human brain tissues (white matter, gray matter, cerebrospinal fluid, tumors and edema). Each selected brain region of interest was characterized with both its mean gray level values and several texture parameters. Multivariate statistical analyses were then applied in order to discriminate each brain tissue type represented by its own set of texture parameters. Texture analysis was previously performed on test objects to evaluate the method dependence on acquisition parameters and consequently the interest of a multicenter evaluation. Even obtained on different sites with their own acquisition routine protocol, MR brain images contain textural features that can reveal discriminant factors for tissue classification and image segmentation. It can also offer additional information in case of undetermined diagnosis or to develop a more accurate tumor grading.     

Optimizing brain MRI protocols in the follow-up of patients with multiple sclerosis T2-weighted MRI of the brain after the administration of gadopentetate dimeglumine

The aim of our study was to determine whether T2-weighted (T2w) MRI of the brain could be performed immediately after the administration of gadopentetate dimeglumine (gadolinium DTPA) in patients with multiple sclerosis (MS) without a loss in image quality or diagnostic reliability. Sixteen patients with clinically diagnosed MS were included in the study. Twenty-four patients with various cerebral pathologies (14 patients with multiple lacunar lesions) were examined in order to exclude masking of T2 hyperintense lesions other than MS lesions. Images of 10 patients without pathological changes served as a control condition for the qualitative analysis. In these 50 patients, T1w and T2w MRI was performed before and after the administration of gadolinium DTPA. Signal intensities were measured within T2 hyperintense cerebral lesions, in T1-enhancing lesions and in normal appearing brain tissue on T2w turbo spin-echo (TSE) sequences. Both quantitative and qualitative analysis did not show significant differences between T2w pre- and postcontrast series. T2w MRI performed prior to and after the administration of gadolinium DTPA provides similar information in patients with MS. With a TR of 3.2 s, not a single lesion was obscured on T2w postcontrast series. Acquisition of T2w MR images immediately after the administration of gadolinium DTPA allows for shorter examination time and assures sufficient time for contrast enhancement in cerebral lesions with a disrupted blood-brain barrier.     

STZ诱导大鼠1型糖尿病进行性脑萎缩的磁共振成像及组织化学研究

1型糖尿病(T1DM)是一种慢性代谢疾病,主要表现为胰岛素分泌量较正常情况下降,会对人体的多个器官和系统造成持续性的损伤．关于糖尿病的横向研究发现糖尿病患者相比于正常人存在着显著的脑萎缩,但关于糖尿病引起的脑萎缩随时间发生进行性改变的研究比较少见．实验采用腹腔注射链脲佐菌素(STZ)来诱导建立大鼠的1型糖尿病模型,运用磁共振成像(MRI)的方法对萎缩的脑区进行定位并在造模后12周和20周两个时间点对脑萎缩的程度进行对比分析,然后运用组织化学染色的方法观察在MRI上出现进行性萎缩的脑区中的神经元所发生的病理改变．MRI的结果表明：STZ诱导的T1DM大鼠相比于正常对照组大鼠出现了显著性的全脑体积、灰质体积和白质体积的萎缩,并且在多个白质脑区和灰质脑区均出现了萎缩程度随着病程的延长而逐渐加重．组织化学染色的结果发现,STZ诱导的T1DM大鼠相对于正常对照组大鼠在体感皮层、运动皮层和海马CA3区,均出现明显的神经元萎缩现象．     

The use of Gd-DOTA in magnetic resonance imaging of experimentally induced mammary tumors

Gd-DOTA contrast enhancement of MR images was evaluated on induced mammary tumors in female rats. A single intravenous injection of the carcinogenic N-nitrosourea ENU was administered to Wistar rats; this simple treatment led to a high percentage of mammary tumors without causing death. All the induced tumors were adenocarcinoma and their heterogeneousness depended on their size. The induced tumors did not have intra- or extravascular inflammatory spaces caused by heterotopic lesions, as is the case with implanted tumors. Before injection of Gd-DOTA, appearance of the patchy internal structure was clearly demonstrated on spin-echo images performed with long repetition times. Three doses of the paramagnetic contrast agent (0.1, 0.2, and 0.5 mmol/kg) were evaluated on two different T1-weighted MR sequences. Images were recorded before and repeatedly after intravenous injection of Gd-DOTA, and signal intensities and relaxation times were measured. On images acquired with the spin-echo 500/28 as well as the inversion-recovery 928/26/300 sequences, the results showed that 0.2 mmol/kg Gd-DOTA was the optimal dose for contrast enhancement and for clear visualization of the heterogeneousness of the mammary tumor.     

MRI gradient fields increase brain mannitol space

Following nephrectomy and intravenous injection of tritiated mannitol, adult male rats were exposed to magnetic resonance imaging (MRI) procedures at 1.5 T, 0.5 T, and 0.3 T. Compared to rats similarly handled but not exposed to MRI procedures, brain mannitol concentration, expressed as a percentage of mean body concentration, was significantly increased at 0.3 T and 0.5 T but not at 1.5 T. At 0.3 T, exposure to gradient-field fluctuations used for imaging increased brain mannitol concentration, but exposures to static main field and pulsed radiofrequency energies did not. Increased brain mannitol associated with gradient-field flux may reflect increased blood-brain barrier permeability or blood volume in brain. MRI effects on brain mannitol space are of uncertain clinical significance, but are consistent with prior evidence of an MRI-induced increase of brain capillary endothelial cell transport observed with horseradish peroxidase. Further studies are needed to confirm these findings and to explore the processes underlying changes in mannitol distribution related to MRI.     

Direct comparison of two methods to measure T1: in vitro and in vivo values by echo-planar imaging and by segmented k-space imaging

We test a hypothesis that proton T(1) is accurately measured independent of the physics inherent to the method. We used two well-validated but quite different imaging methods to measure T(1) in phantoms and in humans; an echo-planar imaging T-one measurement (EPITOME) method, and a segmented k-space acquisition precise and accurate inversion recovery (TurboPAIR) method. Agreement between the methods was generally excellent; the square of the correlation coefficient (r(2)) in phantoms was 0.9996. The r(2) in brain tissue of volunteers was 0.79 overall, and 0.85 if cortical gray matter and corpus callosum were excluded. Nevertheless, small but significant differences were observed between methods in vivo and T(1) measurements were sensitive to tissue type, although measurements could be made comparable. The major difference between the methods is that EPITOME takes 97 s to image 15 slices at low resolution, while TurboPAIR takes 240 s to image one slice at high resolution.     

高场强核磁共振下测量水的自旋晶格弛豫时间

在反转恢复脉冲序列中增加双极性梯度场脉冲以压制辐射阻尼效应,从而使之能够在高场强核磁共振波谱仪(Bruker AV600)中较为准确测量水的自旋-晶格时间.这一方法应用于商品化成像对比剂Gd-DTPA的弛豫率测试,得到的结果和文献相似,证实了该方法的可靠性.进一步应用于新合成成像对比剂TEMDP-EMFs性能的评价.     

Pulsed-wave low-dose ultrasound hyperthermia selectively enhances nanodrug delivery and improves antitumor efficacy for brain metastasis of breast cancer

The clinical application of chemotherapeutics for brain tumors remains a challenge due to limitation of blood-brain barrier/blood-tumor barrier (BBB/BTB). In this study, we investigated the effects of low-dose focused ultrasound hyperthermia (UH) on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer cells (4T1-luc2) expressing firefly luciferase were implanted into mouse striatum as a brain tumor model. The mice were intravenously injected with PLD with/without transcranial pulsed-wave/continuous-wave UH (pUH/cUH) treatment on day-6 after tumor implantation. pUH (frequency: 500 kHz, PRF: 1000 Hz, duty cycle: 50%) was conducted under equal acoustic power (2.2-Watt) and sonication duration (10-min) as cUH. The amounts of doxorubicin accumulated in the normal brain and tumor tissues were measured with fluorometry. The tumor growth responses for the control, pUH, PLD, PLD + cUH, and PLD + pUH groups were evaluated with IVIS. The PLD distribution and cell apoptosis were assessed with immunofluorescence staining. The results showed that pUH significantly enhanced the PLD delivery into brain tumors and the tumor growth was further inhibited by PLD + pUH without damaging the sonicated normal brain tissues. This indicates that low-dose transcranial pUH is a promising method to selectively enhance nanodrug delivery and improve the brain tumor treatment.     

Step-down infusions of Gd-DTPA yield greater contrast-enhanced magnetic resonance images of BBB damage in acute stroke than bolus injections

A rat model of transient suture occlusion of one middle cerebral artery (MCA) was used to create a unilateral reperfused cerebral ischemic infarct with blood-brain barrier (BBB) opening. Opening of the BBB was visualized and quantitated by magnetic resonance (MR) contrast enhancement with a Look-Locker T(1)-weighted sequence either following an intravenous bolus injection (n=7) or during a step-down infusion (n=7) of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA). Blood levels of Gd-DTPA after either input were monitored via changes in sagittal sinus relaxation rate. Blood-to-brain influx constants (K(i)) were calculated by Patlak plots. On the basis of the MRI parameters and lesion size, the ischemic injury was determined to be similar in the two groups. The bolus injection input produced a sharp rise in blood levels of Gd-DTPA that declined quickly, whereas the step-down infusion led to a sharp rise that was maintained relatively constant for the period of imaging. Visual contrast enhancement and signal-to-noise (S/N) ratios were better with the step-down method (S/N=1.8) than with bolus injection (S/N=1.3). The K(i) values were not significantly different between the two groups (P>.05) and were around 0.005 ml/(g min). The major reason for the better imaging of BBB opening by the step-down infusion was the higher amounts of Gd-DTPA in plasma and tissue during most of the experimental period. These results suggest that step-down MR contrast agent (MRCA) administration schedule may be more advantageous for detection and delineation of acute BBB injury than the usually used bolus injections.     

Reaction kinetics analysis to estimate in vivo decay rate of EPR signals of a nitroxide radical in the brain and the inferior vena cava of rats

To clarify the degree of the influence of the peripheral organs on the temporal changes in the electron paramagnetic resonance (EPR) signal intensity of a nitroxide radical permeating the blood-brain barrier, 3-hydroxymethyl-2,2,5,5-tetramethylprrolidine-1-oxyl (hydroxymethyl-PROXYL), in the brain, temporal changes in the EPR signal in the brain or inferior vena cava of rats were measured by an in vivo 700 MHz radio-frequency EPR spectrometer equipped with a bridged loop-gap resonator or a surface-coil-type resonator. In all measurements, good linearity was observed on semilogarithmic plots of the signal intensity against time after the hydroxymethyl-PROXYL injection. From these plots, the reaction rate and the initial level of hydroxymethyl-PROXYL in the brain and the vena cava were calculated. A mathematical model expressing the nitroxide radical concentration in the brain, which is connected to other organs via the circulatory system, was made. With this model and the results of the EPR measurements, the degrees of influence of the nitroxide reduction in the brain and the other organs were simulated. It was found that the reaction rate (equal to log2/half-life) of hydroxymethyl-PROXYL observed in the brain reflected the reduction of hydroxymethyl-PROXYL there and was not influenced by the reduction in other organs.     

Short-term evolution of individual enhancing MS lesions studied with magnetization transfer imaging.

We performed serial monthly magnetization transfer (MT) imaging to evaluate the prevalence and evolution of structural changes in individual enhancing lesions from patients with multiple sclerosis (MS). Every 4 weeks for 3 months, we obtained dual echo, magnetization transfer (MT) imaging and, 5 min after SD (0.1 mmol/kg) gadolinium-DTPA injection, T1-weighted scans from 10 patients with early relapsing-remitting MS. We measured the MT ratio (MTR) of enhancing lesions seen on the entry scans on co-registered quantitative MTR images at entry and during the follow up. Fourty-two enhancing lesions were identified on the entry scans. According to the "maximal random fluctuation" detected for the normal-appearing white matter MTR values, 16 (38%) lesions were classified as "increasing MTR" lesions, 21 (50%) as "stable MTR" lesions, and 5 (12%) as "decreasing MTR" lesions. The classification of the lesions after the first month of follow up strongly predicted the classification at the end of the follow up (chi squared = 20.35, p = 0.0004). These results indicate that the enhancing lesion population in MS is heterogeneous, and that reparative mechanisms occurring after blood-brain barrier opening are not efficient in only a minority of the enhancing lesions from patients with early relapsing-remitting MS.     

Comparison of dual-echo DSC-MRI- and DCE-MRI-derived contrast agent kinetic parameters

The application of dynamic susceptibility contrast (DSC) MRI methods to assess brain tumors is often confounded by the extravasation of contrast agent (CA). Disruption of the blood-brain barrier allows CA to leak out of the vasculature leading to additional T(1), T(2) and T(2) relaxation effects in the extravascular space, thereby affecting the signal intensity time course in a complex manner. The goal of this study was to validate a dual-echo DSC-MRI approach that separates and quantifies the T(1) and T(2) contributions to the acquired signal and enables the estimation of the volume transfer constant, K(trans), and the volume fraction of the extravascular extracellular space, v(e). To test the validity of this approach, DSC-MRI- and dynamic contrast enhanced (DCE) MRI-derived K(trans) and v(e) estimates were spatially compared in both 9L and C6 rat brain tumor models. A high degree of correlation (concordance correlation coefficients >0.83, Pearson's r>0.84) and agreement was found between the DSC-MRI- and DCE-MRI-derived measurements. These results indicate that dual-echo DSC-MRI can be used to simultaneously extract reliable DCE-MRI kinetic parameters in brain tumors in addition to conventional blood volume and blood flow metrics.     

Optimization of 3D MP-RAGE for neonatal brain imaging at 3.0 T

Three-dimensional (3D) magnetic resonance imaging (MRI) has shown great potential for studying the impact of prematurity and pathology on brain development. We have investigated the potential of optimized T1-weighted 3D magnetization-prepared rapid gradient-echo imaging (MP-RAGE) for obtaining contrast between white matter (WM) and gray matter (GM) in neonates at 3 T. Using numerical simulations, we predicted that the inversion time (TI) for obtaining strongest contrast at 3 T is approximately 2 s for neonates, whereas for adults, this value is approximately 1.3 s. The optimal neonatal TI value was found to be insensitive to reasonable variations of the assumed T1 relaxation times. The maximum theoretical contrast for neonates was found to be approximately one third of that for adults. Using the optimized TI values, MP-RAGE images were obtained from seven neonates and seven adults at 3 T, and the contrast-to-noise ratio (CNR) was measured for WM versus five GM regions. Compared to adults, neonates exhibited lower CNR between cortical GM and WM and showed a different pattern of regional variation in CNR. These results emphasize the importance of sequence optimization specifically for neonates and demonstrate the challenge in obtaining strong contrast in neonatal brain with T1-weighted 3D imaging.     

西洋参-石菖蒲对糖尿病认知障碍大鼠学习记忆相关脑区的影响

本文探究了西洋参-石菖蒲（X-S）药液对糖尿病认知障碍（DACD）大鼠学习记忆相关脑区的影响．腹腔注射链脲佐菌素（STZ）诱导糖尿病大鼠模型,并将动物分为糖尿病组和X-S组,STZ注射7天后给予X-S药,每日1次,连续113天;于STZ注射80天后采用Morris水迷宫方法筛选DACD和非认知障碍（DNCD）大鼠;120天后运用磁共振成像（MRI）技术扫描大鼠全脑,利用感兴趣区（ROI）法和基于体素形态学（VBM）法对各组大鼠大脑灰质和白质进行体积和密度的分析;并通过苏木精-伊红（HE）染色观察大鼠海马神经元的形态结构．ROI分析法显示：与DACD组相比,X-S组大鼠左侧颞叶联合皮质体积减小（p<0.05）;VBM分析法显示：与DACD组相比,X-S组大鼠海马CA1、CA3区及其它脑区的体积和密度或增高或降低（p<0.005）．HE染色结果显示：与DACD组相比,X-S组大鼠海马CA1、CA3区的细胞固缩及排列紊乱减轻．结果表明X-S药液对DACD大鼠与学习记忆相关的海马及其它脑区存在双向调节,从而发挥学习记忆能力的改善作用．     

A fast 3D look-locker method for volumetric T1 mapping.

We introduce a fast technique, based on the principles of the 2D Look-Locker T1 measurement scheme, to rapidly acquire the data for accurate maps of T1 in three dimensions. The acquisition time has been shortened considerably by segmenting the acquisition of the k(y) phase encode lines. Using this technique, the data for a 256 x 128 x 32 volumetric T1 measurement can be acquired in 7.6 min. T1 measurements made in phantoms with T1s between 200 and 1200 ms had an accuracy of 4% and a reproducibility of 3.5%. Measurements of T1 made in normal brain using the fast 3D sequence corresponded well with inversion-recovery fast spin-echo measurements.