弥散张量成像在轻度认知功能障碍中的应用

轻度认知功能障碍（MCI）目前已经成为严重影响老年人健康的疾病，早期具有可逆性。近年来弥散张量成像（DTI）以其定量显示脑白质纤维束的优势，越来越多的应用于临床，成为了研究的热点。目前研究表明，MCI患者海马、穹隆、扣带回和胼胝体的DTI指标变化明显，可用于MCI的早期识别和病情评估及预测，且多个指标联用可能增加其准确性。MCI患者DTI表现与认知功能的下降程度具有相关性，尤其与记忆功能的相关性较为确定。MCI亚型中，遗忘型MCI （aMCI）发展为阿尔茨海默病（AD）的风险更高，其部分各向异性（FA）值越低、平均弥散度（ADC）值越高预示着转化为AD的可能性越大；DTI技术对AD与MCI患者脑白质的差异较为灵敏，AD的脑白质病变范围更广、程度更重。但目前关于DTI在MCI中的应用尚存在诸多问题，尚需进一步研究。     

Hierarchical non‐negative matrix factorization to characterize brain tumor heterogeneity using multi‐parametric MRI

Tissue characterization in brain tumors and, in particular, in high‐grade gliomas is challenging as a result of the co‐existence of several intra‐tumoral tissue types within the same region and the high spatial heterogeneity. This study presents a method for the detection of the relevant tumor substructures (i.e. viable tumor, necrosis and edema), which could be of added value for the diagnosis, treatment planning and follow‐up of individual patients. Twenty‐four patients with glioma [10 low‐grade gliomas (LGGs), 14 high‐grade gliomas (HGGs)] underwent a multi‐parametric MRI (MP‐MRI) scheme, including conventional MRI (cMRI), perfusion‐weighted imaging (PWI), diffusion kurtosis imaging (DKI) and short‐TE ¹H MRSI. MP‐MRI parameters were derived: T₂, T₁ + contrast, fluid‐attenuated inversion recovery (FLAIR), relative cerebral blood volume (rCBV), mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK) and the principal metabolites lipids (Lip), lactate (Lac), N‐acetyl‐aspartate (NAA), total choline (Cho), etc. Hierarchical non‐negative matrix factorization (hNMF) was applied to the MP‐MRI parameters, providing tissue characterization on a patient‐by‐patient and voxel‐by‐voxel basis. Tissue‐specific patterns were obtained and the spatial distribution of each tissue type was visualized by means of abundance maps. Dice scores were calculated by comparing tissue segmentation derived from hNMF with the manual segmentation by a radiologist. Correlation coefficients were calculated between each pathologic tissue source and the average feature vector within the corresponding tissue region. For the patients with HGG, mean Dice scores of 78%, 85% and 83% were obtained for viable tumor, the tumor core and the complete tumor region. The mean correlation coefficients were 0.91 for tumor, 0.97 for necrosis and 0.96 for edema. For the patients with LGG, a mean Dice score of 85% and mean correlation coefficient of 0.95 were found for the tumor region. hNMF was also applied to reduced MRI datasets, showing the added value of individual MRI modalities. Copyright © 2015 John Wiley & Sons, Ltd.     

Tractography of the optic radiation: a repeatability and reproducibility study

Our main objective was to evaluate the repeatability and reproducibility of optic radiation (OR) reconstruction from diffusion MRI (dMRI) data. 14 adults were scanned twice with the same 60‐direction dMRI sequence. Peaks in the diffusion profile were estimated with the single tensor (ST), Q‐ball (QSH) and persistent angular structure (PAS) methods. Segmentation of the OR was performed by two experimenters with probabilistic tractography based on a manually drawn region‐of‐interest (ROI) protocol typically employed for OR segmentation, with both standard and extended sets of ROIs. The repeatability and reproducibility were assessed by calculating the intra‐class correlation coefficient (ICC) of intra‐ and inter‐rater experiments, respectively. ICCs were calculated for commonly used dMRI metrics (FA, MD, AD, RD) and anatomical dimensions of the optic radiation (distance from Meyer's loop to the temporal pole, ML‐TP), as well as the Dice similarity coefficient (DSC) between the raters’ OR segmentation. Bland–Altman plots were also calculated to investigate bias and variability in the reproducibility measurements. The OR was successfully reconstructed in all subjects by both raters. The ICC was found to be in the good to excellent range for both repeatability and reproducibility of the dMRI metrics, DSC and ML‐TP distance. The Bland–Altman plots did not show any apparent systematic bias for any quantities. Overall, higher ICC values were found for the multi‐fiber methods, QSH and PAS, and for the standard set of ROIs. Considering the good to excellent repeatability and reproducibility of all the quantities investigated, these findings support the use of multi‐fiber OR reconstruction with a limited number of manually drawn ROIs in clinical applications utilizing either OR microstructure characterization or OR dimensions, as is the case in neurosurgical planning for temporal lobectomy. Copyright © 2015 John Wiley & Sons, Ltd.     

A brief report on MRI investigation of experimental traumatic brain injury

Traumatic brain injury is a major cause of death and disability. This is a brief report based on a symposium presentation to the2014 Chinese Neurotrauma Association Meeting in San Francisco, USA. It covers the work from our laboratory in applying multimodal MRI to study experimental traumatic brain injury in rats with comparisons made to behavioral tests and histology. MRI protocols include structural, perfusion, manganese-enhanced, diffusion-tensor MRI, and MRI of blood-brain barrier integrity and cerebrovascular reactivity.     

Intrinsic diffusion sensitivity of the balanced steady‐state free precession (bSSFP) imaging sequence

The purpose of this work was to analyze the intrinsic diffusion sensitivity of the balanced steady‐state free precession (bSSFP) imaging sequence, meaning the observation of diffusion‐induced attenuation of the bSSFP steady‐state signal due to the imaging gradients. Although these diffusion effects are usually neglected for most clinical gradient systems, such strong gradient systems are employed for high resolution imaging of small animals or MR Microscopy. The impact on the bSSFP signal of the imaging gradients characterized by their b‐values was analyzed with simulations and experiments at a 7T animal scanner using a gradient system with maximum gradient amplitude of approx. 700 mT/m. It was found that the readout gradients have a stronger impact on the attenuation than the phase encoding gradients. Also, as the PE gradients are varying with each repetition interval, the diffusion effects induce strong modulations of the bSSFP signal over the sequence repetition cycles depending on the phase encoding gradient table. It is shown that a signal gain can be obtained through a change of flip angle as a new optimal flip angle maximizing the signal can be defined. The dependency of the diffusion effects on relaxation times and b‐values were explored with simulations. The attenuation increases with T₂. In conclusion, diffusion attenuation of the bSSFP signal becomes significant for high resolution imaging voxel size (roughly < 100 μm) of long T₂ substances. Copyright © 2015 John Wiley & Sons, Ltd.     

Using EMG to deliver lumbar dynamic electrical stimulation to facilitate cortico-spinal excitability

BackgroundPotentiation of synaptic activity in spinal networks is reflected in the magnitude of modulation of motor responses evoked by spinal and cortical input. After spinal cord injury, motor evoked responses can be facilitated by pairing cortical and peripheral nerve stimuli.ObjectiveTo facilitate synaptic potentiation of cortico-spinal input with epidural electrical stimulation, we designed a novel neuromodulation method called dynamic stimulation (DS), using patterns derived from hind limb EMG signal during stepping.MethodsDS was applied dorsally to the lumbar enlargement through a high-density epidural array composed of independent platinum-based micro-electrodes.ResultsIn fully anesthetized intact adult rats, at the interface array/spinal cord, the temporal and spatial features of DS neuromodulation affected the entire lumbosacral network, particularly the most rostral and caudal segments covered by the array. DS induced a transient (at least 1 min) increase in spinal cord excitability and, compared to tonic stimulation, generated a more robust potentiation of the motor output evoked by single pulses applied to the spinal cord. When sub-threshold pulses were selectively applied to a cortical motor area, EMG responses from the contralateral leg were facilitated by the delivery of DS to the lumbosacral cord. Finally, based on motor-evoked responses, DS was linked to a greater amplitude of motor output shortly after a calibrated spinal cord contusion.ConclusionCompared to traditional tonic waveforms, DS amplifies both spinal and cortico-spinal input aimed at spinal networks, thus significantly increasing the potential and accelerating the rate of functional recovery after a severe spinal lesion.     

Multiparametric MRI for early identification of therapeutic response in recurrent glioblastoma treated with immune checkpoint inhibitors

BackgroundPhysiologic changes quantified by diffusion and perfusion MRI have shown utility in predicting treatment response in glioblastoma (GBM) patients treated with cytotoxic therapies. We aimed to investigate whether quantitative changes in diffusion and perfusion after treatment by immune checkpoint inhibitors (ICIs) would determine 6-month progression-free survival (PFS6) in patients with recurrent GBM.MethodsInclusion criteria for this retrospective study were: (i) diagnosis of recurrent GBM treated with ICIs and (ii) availability of diffusion and perfusion in pre and post ICI MRI (iii) at ≥6 months follow-up from treatment. After co-registration, mean values of the relative apparent diffusion coefficient (rADC), K^trans (volume transfer constant), Ve (extravascular extracellular space volume) and Vp (plasma volume), and relative cerebral blood volume (rCBV) were calculated from a volume-of-interest of the enhancing tumor. Final assignment of stable/improved versus progressive disease was determined on 6-month follow-up using modified Response Assessment in Neuro-Oncology criteria.ResultsOut of 19 patients who met inclusion criteria and follow-up (mean ± SD: 7.8 ± 1.4 mo), 12 were determined to have tumor progression, while 7 had treatment response after 6 months of ICI treatment. Only interval change of rADC was suggestive of treatment response. Patients with treatment response (6/7: 86%) had interval increased rADC, while 11/12 (92%) with tumor progression had decreased rADC (P = 0.001). Interval change in rCBV, K^trans, Vp, and Ve were not indicative of treatment response within 6 months.ConclusionsIn patients with recurrent GBM, interval change in rADC is promising in assessing treatment response versus progression within the first 6 months following ICI treatment.Key Points• In recurrent GBM treated with ICIs, interval change in rADC suggests early treatment response.• Interval change in rADC can be used as an imaging biomarker to determine PFS6.• Interval change in MR perfusion and permeability measures do not suggest ICI treatment response.