Stratification of the aggressiveness of prostate cancer using pre‐biopsy multiparametric MRI (mpMRI)

Risk stratification, based on the Gleason score (GS) of a prostate biopsy, is an important decision‐making tool in prostate cancer management. As low‐grade disease may not need active intervention, the ability to identify aggressive cancers on imaging could limit the need for prostate biopsies. We assessed the ability of multiparametric MRI (mpMRI) in pre‐biopsy risk stratification of men with prostate cancer. One hundred and twenty men suspected to have prostate cancer underwent mpMRI (diffusion MRI and MR spectroscopic imaging) prior to biopsy. Twenty‐six had cancer and were stratified into three groups based on GS: low grade (GS ≤ 6), intermediate grade (GS = 7) and high grade (GS ≥ 8). A total of 910 regions of interest (ROIs) from the peripheral zone (PZ, range 25–45) were analyzed from these 26 patients. The metabolite ratio [citrate/(choline + creatine)] and apparent diffusion coefficient (ADC) of voxels were calculated for the PZ regions corresponding to the biopsy cores and compared with histology. The median metabolite ratios for low‐grade, intermediate‐grade and high‐grade cancer were 0.29 (range: 0.16, 0.61), 0.17 (range: 0.13, 0.32) and 0.13 (range: 0.05, 0.23), respectively (p = 0.004). The corresponding mean ADCs (×10^–3 mm²/s) for low‐grade, intermediate‐grade and high‐grade cancer were 0.99 ± 0.08, 0.86 ± 0.11 and 0.69 ± 0.12, respectively (p < 0.0001). The combined ADC and metabolite ratio model showed strong discriminatory ability to differentiate subjects with GS ≤ 6 from subjects with GS ≥ 7 with an area under the curve of 94%. These data indicate that pre‐biopsy mpMRI may stratify PCa aggressiveness noninvasively. As the recent literature data suggest that men with GS ≤ 6 cancer may not need radical therapy, our data may help limit the need for biopsy and allow informed decision making for clinical intervention. Copyright © 2015 John Wiley & Sons, Ltd.     

Fast and simplified mapping of mean axon diameter using temporal diffusion spectroscopy

Mapping axon diameter is of interest for the potential diagnosis and monitoring of various neuronal pathologies. Advanced diffusion‐weighted MRI methods have been developed to measure mean axon diameters non‐invasively, but suffer major drawbacks that prevent their direct translation into clinical practice, such as complex non‐linear data fitting and, more importantly, long scanning times that are usually not tolerable for most human subjects. In the current study, temporal diffusion spectroscopy using oscillating diffusion gradients was used to measure mean axon diameters with high sensitivity to small axons in the central nervous system. Axon diameters have been found to be correlated with a novel metric, DDR_⊥ (the rate of dispersion of the perpendicular diffusion coefficient with gradient frequency), which is a model‐free quantity that does not require complex data analyses and can be obtained from two diffusion coefficient measurements in clinically relevant times with conventional MRI machines. A comprehensive investigation including computer simulations and animal experiments ex vivo showed that measurements of DDR_⊥ agree closely with histological data. In humans in vivo, DDR_⊥ was also found to correlate well with reported mean axon diameters in human corpus callosum, and the total scan time was only about 8 min. In conclusion, DDR_⊥ may have potential to serve as a fast, simple and model‐free approach to map the mean axon diameter of white matter in clinics for assessing axon diameter changes. Copyright © 2016 John Wiley & Sons, Ltd.     

Diffusional kurtosis MRI of the lower leg: changes caused by passive muscle elongation and shortening

Diffusional kurtosis MRI (DKI) quantifies the deviation of water diffusion from a Gaussian distribution. We investigated the influence of passive elongation and shortening of the lower leg muscles on the DKI parameters D (diffusion coefficient) and K (kurtosis). After approval by the local ethics committee, eight healthy volunteers (age, 29.1 ± 2.9 years) underwent MRI of the lower leg at 3 T. Diffusion‐weighted images were acquired with 10 different b values at three ankle positions (passive dorsiflexion 10°, neutral position 0°, passive plantar flexion 40°). Parametrical maps of D and K were obtained by voxel‐wise fitting of the signal intensities using a non‐linear Levenberg–Marquardt algorithm. D and K were measured in the tibialis anterior, medial and lateral gastrocnemius, and soleus muscles. In the neutral position, D and K values were in the range between 1.66–1.79 × 10^–3 mm²/s and 0.21–0.39, respectively. D and K increased with passive shortening, and decreased with passive elongation, which could also be illustrated on the parametrical maps. In dorsiflexion, D (p < 0.01) and K (p = 0.036) were higher in the tibialis anterior than in the medial gastrocnemius. In plantar flexion, the opposite was found for K (p = 0.035). DKI parameters in the lower leg muscles are significantly influenced by the ankle joint position, indicating that the diffusion of water molecules in skeletal muscle deviates from a Gaussian distribution depending on muscle tonus. Copyright © 2016 John Wiley & Sons, Ltd.     

Diffusion‐prepared stimulated‐echo turbo spin echo (DPsti‐TSE): An eddy current‐insensitive sequence for three‐dimensional high‐resolution and undistorted diffusion‐weighted imaging

In this study, we present a new three‐dimensional (3D), diffusion‐prepared turbo spin echo sequence based on a stimulated‐echo read‐out (DPsti‐TSE) enabling high‐resolution and undistorted diffusion‐weighted imaging (DWI). A dephasing gradient in the diffusion preparation module and rephasing gradients in the turbo spin echo module create stimulated echoes, which prevent signal loss caused by eddy currents. Near to perfect agreement of apparent diffusion coefficient (ADC) values between DPsti‐TSE and diffusion‐weighted echo planar imaging (DW‐EPI) was demonstrated in both phantom transient signal experiments and phantom imaging experiments. High‐resolution and undistorted DPsti‐TSE was demonstrated in vivo in prostate and carotid vessel wall. 3D whole‐prostate DWI was achieved with four b values in only 6 min. Undistorted ADC maps of the prostate peripheral zone were obtained at low and high imaging resolutions with no change in mean ADC values [(1.60 ± 0.10) × 10^?3 versus (1.60 ± 0.02) × 10^?3 mm²/s]. High‐resolution 3D DWI of the carotid vessel wall was achieved in 12 min, with consistent ADC values [(1.40 ± 0.23) × 10^?3 mm²/s] across different subjects, as well as slice locations through the imaging volume. This study shows that DPsti‐TSE can serve as a robust 3D diffusion‐weighted sequence and is an attractive alternative to the traditional two‐dimensional DW‐EPI approaches.     

Diffusion parameter mapping with the combined intravoxel incoherent motion and kurtosis model using artificial neural networks at 3 T

Artificial neural networks (ANNs) were used for voxel‐wise parameter estimation with the combined intravoxel incoherent motion (IVIM) and kurtosis model facilitating robust diffusion parameter mapping in the human brain. The proposed ANN approach was compared with conventional least‐squares regression (LSR) and state‐of‐the‐art multi‐step fitting (LSR‐MS) in Monte‐Carlo simulations and in vivo in terms of estimation accuracy and precision, number of outliers and sensitivity in the distinction between grey (GM) and white (WM) matter. Both the proposed ANN approach and LSR‐MS yielded visually increased parameter map quality. Estimations of all parameters (perfusion fraction f, diffusion coefficient D, pseudo‐diffusion coefficient D*, kurtosis K) were in good agreement with the literature using ANN, whereas LSR‐MS resulted in D* overestimation and LSR yielded increased values for f and D*, as well as decreased values for K. Using ANN, outliers were reduced for the parameters f (ANN, 1%; LSR‐MS, 19%; LSR, 8%), D* (ANN, 21%; LSR‐MS, 25%; LSR, 23%) and K (ANN, 0%; LSR‐MS, 0%; LSR, 15%). Moreover, ANN enabled significant distinction between GM and WM based on all parameters, whereas LSR facilitated this distinction only based on D and LSR‐MS on f, D and K. Overall, the proposed ANN approach was found to be superior to conventional LSR, posing a powerful alternative to the state‐of‐the‐art method LSR‐MS with several advantages in the estimation of IVIM–kurtosis parameters, which might facilitate increased applicability of enhanced diffusion models at clinical scan times.     

Can increased spatial resolution solve the crossing fiber problem for diffusion MRI?

It is now widely recognized that voxels with crossing fibers or complex geometrical configurations present a challenge for diffusion MRI (dMRI) reconstruction and fiber tracking, as well as microstructural modeling of brain tissues. This “crossing fiber” problem has been estimated to affect anywhere from 30% to as many as 90% of white matter voxels, and it is often assumed that increasing spatial resolution will decrease the prevalence of voxels containing multiple fiber populations. The aim of this study is to estimate the extent of the crossing fiber problem as we progressively increase the spatial resolution, with the goal of determining whether it is possible to mitigate this problem with higher resolution spatial sampling. This is accomplished using ex vivo MRI data of the macaque brain, followed by histological analysis of the same specimen to validate these measurements, as well as to extend this analysis to resolutions not yet achievable in practice with MRI. In both dMRI and histology, we find unexpected results: the prevalence of crossing fibers increases as we increase spatial resolution. The problem of crossing fibers appears to be a fundamental limitation of dMRI associated with the complexity of brain tissue, rather than a technical problem that can be overcome with advances such as higher fields and stronger gradients.     

Multi‐centre reproducibility of diffusion MRI parameters for clinical sequences in the brain

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra‐voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences. An ice–water phantom and nine healthy volunteers were scanned across fives centres on eight scanners (four Siemens 1.5T, four Philips 3T). The mean ADC, IVIM parameters (diffusion coefficient D and perfusion fraction f) and DTI parameters (mean diffusivity MD and fractional anisotropy FA), were measured in grey matter, white matter and specific brain sub‐regions. A mixed effect model was used to measure the intra‐ and inter‐scanner coefficient of variation (CV) for each of the five parameters. ADC, D, MD and FA had a good intra‐ and inter‐scanner reproducibility in both grey and white matter, with a CV ranging between 1% and 7.4%; mean 2.6%. Other brain regions also showed high levels of reproducibility except for small structures such as the choroid plexus. The IVIM parameter f had a higher intra‐scanner CV of 8.4% and inter‐scanner CV of 24.8%. No major difference in the inter‐scanner CV for ADC, D, MD and FA was observed when analysing the 1.5T and 3T scanners separately. ADC, D, MD and FA all showed good intra‐scanner reproducibility, with the inter‐scanner reproducibility being comparable or faring slightly worse, suggesting that using data from multiple scanners does not have an adverse effect compared with using data from the same scanner. The IVIM parameter f had a poorer inter‐scanner CV when scanners of different field strengths were combined, and the parameter was also affected by the scan acquisition resolution. This study shows that the majority of diffusion MRI derived parameters are robust across 1.5T and 3T scanners and suitable for use in multi‐centre clinical studies and trials. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.     

应用整体组织病理切片评估相关辅助检查在前列腺癌定位诊断中的价值

目的:探讨以前列腺癌根治术后整体组织病理切片(前列腺大切片)作为"金标准"分别评估DRE、前列腺穿刺活检、MRI、DWI在前列腺癌定位诊断中的价值。方法:回顾性分析2009年10月～2010年3月行腹腔镜前列腺癌根治术19例患者临床资料,除外未行MRI/DWI检查、前列腺手术史、已行内分泌治疗等患者9例,符合条件患者10例,于前列腺癌根治术前收集患者的DRE、前列腺穿刺活检、MRI、DWI资料,术后将前列腺标本制成前列腺大切片。应用"六分区法"对前列腺进行分区,DRE检查记录前列腺结节所在区域,前列腺穿刺活检12针依位置编号将阳性者归入相应区域,与术后整体组织病理进行比对。两位阅片者"盲法"进行阅MRI和MRI/DWI片,每个分区分为5档进行评价:1.正常;2.可能正常;3.不确定;4.可能是癌;5.肯定是癌,当两位阅片者所得结果的平均值≥4时,认定该区域是MRI或MRI+DWI评估为前列腺癌的区域。结果:在10例前列腺癌患者共60个分区中前列腺大切片证实的前列腺癌区域为27个(45%),基底部、中部、尖部的前列腺癌区域分别为8个(40%)、11个(55%)和8个(40%),前列腺癌呈明显的多灶性分布。DRE定位诊断前列腺癌的敏感性、特异性分别为29.6%、72.7%,低于其他检查方法,前列腺穿刺活检定位诊断前列腺癌的敏感性、特异性分别为55.6%、81.8%,与MRI的诊断价值类似(51.9%和84.9%),引入DWI参与前列腺癌的定位诊断,可维持特异性不变的情况下,提高MRI的敏感性至77.8%。对于前列腺尖部、中部MRI诊断的敏感性较差(37.5%和45.5%),但特异性和阳性预测值高(100%和100%),引入DWI可将前列腺尖部、中部MRI诊断的敏感性提高至75%和81.8%。结论:MRI在前列腺癌定位中的价值与前列腺穿刺活检相似,但明显优于DRE;引入DWI可以明显提高MRI定位诊断前列腺癌的敏感性,特别是对于前列腺尖部和中部的肿瘤。     

The adipogenic potential of various extracellular matrices under the influence of an angiogenic growth factor combination in a mouse tissue engineering chamber

The extracellular matrix (ECM) Matrigel™ has frequently and successfully been used to generate new adipose tissue experimentally, but is unsuitable for human application. This study sought to compare the adipogenic potential of a number of alternative, biologically derived or synthetic ECMs with potential for human application, with and without growth factors and a small fat autograft. Eight groups, with six severe combined immunodeficient (SCID) mice per group, were created with bilateral chambers (silicone tubes) implanted around the epigastric vascular pedicle, with one chamber/animal containing a 5 mg fat autograft. Two animal groups were created for each of four ECMs (Matrigel™, Myogel, Cymetra® and PuraMatrix™) which filled the bilateral chambers. One group/ECM had no growth factors added to chambers whilst the other group had growth factors (GFs) (vascular endothelial growth factor-A (VEGF-A) plus fibroblast growth factor-2 (FGF-2) plus platelet-derived growth factor-BB (PDGF-BB)) added to both chambers. At 6 weeks, chamber tissue was morphometrically assessed for percent and absolute adipose tissue volume. Overall, the triple GF regime significantly increased percent¹ and absolute^# adipose tissue volume (p < 0.0005^1#) compared to chambers without triple GF treatment. The fat autograft also significantly increased percent (p < 0.0005) and absolute (p < 0.011) adipose tissue volume. Cymetra® (human collagen) constructs yielded the largest total tissue and absolute adipose tissue volume. We found that the pro-angiogenic FGF-2, VEGF-A and PDGF-BB combination in ECMs of synthetic and biological origin produced an overall significantly increased adipose tissue volume at 6 weeks and may have clinical application, particularly with Cymetra.