Quantitative magnetic resonance imaging for focal liver lesions: bridging the gap between research and clinical practice

Magnetic resonance imaging (MRI) is highly important for the detection, characterization, and follow-up of focal liver lesions. Several quantitative MRI-based methods have been proposed in addition to qualitative imaging interpretation to improve the diagnostic work-up and prognostics in patients with focal liver lesions. This includes DWI with apparent diffusion coefficient measurements, intravoxel incoherent motion, perfusion imaging, MR elastography, and radiomics. Multiple research studies have reported promising results with quantitative MRI methods in various clinical settings. Nevertheless, applications in everyday clinical practice are limited. This review describes the basic principles of quantitative MRI-based techniques and discusses the main current applications and limitations for the assessment of focal liver lesions.     

IVIM-DWI技术在肝脏弥漫性病变中的研究进展

在生物组织中体素内不相干运动(IVIM)包括体素内水分子扩散和微循环灌注,IVIM双指数模型可以精确描述DWI信号衰减与b值的关系,分别获取反映组织水分子扩散和微循环灌注的参数。近年来,IVIM成像在肝脏弥漫性病变的检测与分级中应用越来越多。主要阐述肝脏IVIM成像的原理、影响因素及可重复性以及在弥漫性病变中的诊断价值。     

磁共振扩散及灌注成像技术在新生儿急性缺氧缺血性脑病中的应用

缺氧缺血性脑病在新生儿中发病率较高,其致残及致死率居高不下,MRI已成为诊断HIE及评估预后的主要影像检查方法。近年来,一些新型MRI技术,例如扩散加权成像、扩散张量成像、扩散峰度成像、动脉自旋标记成像、体素内不相干运动等在扩散及灌注成像方面有了显著发展,能够更好地反映HIE的病理改变。就MRI扩散及灌注成像新技术在HIE中的成像特点及应用进行综述。     

Intravoxel incoherent motion imaging of tumor microenvironment in locally advanced breast cancer

Diffusion‐weighted imaging plays important roles in cancer diagnosis, monitoring, and treatment. Although most applications measure restricted diffusion by tumor cellularity, diffusion‐weighted imaging is also sensitive to vascularity through the intravoxel incoherent motion effect. Hypervascularity can confound apparent diffusion coefficient measurements in breast cancer. We acquired multiple b‐value diffusion‐weighted imaging at 3 T in a cohort of breast cancer patients and performed biexponential intravoxel incoherent motion analysis to extract tissue diffusivity (D_t), perfusion fraction (f_p), and pseudodiffusivity (D_p). Results indicated significant differences between normal fibroglandular tissue and malignant lesions in apparent diffusion coefficient mean (±standard deviation) values (2.44 ± 0.30 vs. 1.34 ± 0.39 μm²/msec, P < 0.01) and D_t (2.36 ± 0.38 vs. 1.15 ± 0.35 μm²/msec, P < 0.01). Lesion diffusion‐weighted imaging signals demonstrated biexponential character in comparison to monoexponential normal tissue. There is some differentiation of lesion subtypes (invasive ductal carcinoma vs. other malignant lesions) with f_p (10.5 ± 5.0% vs. 6.9 ± 2.9%, P = 0.06), but less so with D_t (1.14 ± 0.32 μm²/msec vs. 1.18 ± 0.52 μm²/msec, P = 0.88) and D_p (14.9 ± 11.4 μm²/msec vs. 16.1 ± 5.7 μm²/msec, P = 0.75). Comparison of intravoxel incoherent motion biomarkers with contrast enhancement suggests moderate correlations. These results suggest the potential of intravoxel incoherent motion vascular and cellular biomarkers for initial grading, progression monitoring, or treatment assessment of breast tumors. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

同时多层成像技术联合肝脏MR扩散成像的应用及展望

同时多层（SMS）成像技术与多种MRI序列联合应用可明显缩短成像时间。MR扩散成像,如常规扩散加权成像（DWI）、体素内不相干运动成像（IVIM）、扩散张量成像（DTI）和扩散峰度成像（DKI）能反映组织内水分子扩散、血流灌注、组织结构复杂性等微观特征,在肝脏病变检测和辅助定性中有重要价值。SMS与MR扩散成像联合后可明显缩短成像时间,利于各种MR扩散成像在肝脏中的广泛应用。综述SMS对肝脏扩散成像扫描速度的提升效率、对影像质量和定量参数的影响,以期推动SMS成像技术在临床中的广泛应用。     

Error model for reduction of cardiac and respiratory motion effects in quantitative liver DW‐MRI

Diffusion‐weighted images of the liver exhibit signal dropout from cardiac and respiratory motion, particularly in the left lobe. These artifacts cause bias and variance in derived parameters that quantify intravoxel incoherent motion. Many models of diffusion have been proposed, but few separate attenuation from diffusion or perfusion from that of bulk motion. The error model proposed here (Beta*LogNormal) is intended to accomplish that separation by modeling stochastic attenuation from bulk motion as multiplication by a Beta‐distributed random variate. Maximum likelihood estimation with this error model can be used to derive intravoxel incoherent motion parameters separate from signal dropout, and does not require a priori specification of parameters to do so. Liver intravoxel incoherent motion parameters were derived for six healthy subjects under this error model and compared with least‐squares estimates. Least‐squares estimates exhibited bias due to cardiac and respiratory gating and due to location within the liver. Bias from these factors was significantly reduced under the Beta*LogNormal model, as was within‐organ parameter variance. Similar effects were appreciable in diffusivity maps in two patients with focal liver lesions. These results suggest that, relative to least‐squares estimation, the Beta*LogNormal model accomplishes the intended reduction of bias and variance from bulk motion in liver diffusion imaging. Magn Reson Med 70:1460–1469, 2013. © 2012 Wiley Periodicals, Inc.     

Utility of Intravoxel Incoherent Motion MR Imaging for Distinguishing Recurrent Metastatic Tumor from Treatment Effect following Gamma Knife Radiosurgery: Initial Experience

BACKGROUND AND PURPOSE:Intravoxel incoherent motion MR imaging can simultaneously measure the diffusion and perfusion characteristics of brain tumors. Our aim was to determine the utility of intravoxel incoherent motion–derived perfusion and diffusion parameters for assessing the treatment response of metastatic brain tumor following gamma knife radiosurgery.MATERIALS AND METHODS:Ninety-one consecutive patients with metastatic brain tumor treated with gamma knife radiosurgery were assessed by using intravoxel incoherent motion imaging. Two readers independently calculated the 90th percentile and the 10th percentile histogram cutoffs for perfusion, normalized CBV, diffusion, and ADC. Areas under the receiver operating characteristic curve and interreader agreement were assessed.RESULTS:With the combination of the 90th percentile histogram cutoff for perfusion and the 10th percentile histogram cutoff for diffusion, the sensitivity and specificity for differentiating recurrent tumor and treatment were 79.5% and 92.3% for reader 1 and 84.6% and 94.2% for reader 2, respectively. With the combination of the 90th percentile histogram cutoff for normalized CBV and the 10th percentile histogram cutoff for ADC, the sensitivity and specificity for differentiating recurrent tumor and treatment were 69.2% and 100.0% for reader 1 and 74.3% and 100.0% for reader 2, respectively. Compared with the combination of 90th percentile histogram cutoff for normalized CBV and the 10th percentile histogram cutoff for ADC, adding intravoxel incoherent motion to 90th percentile histogram cutoff for normalized CBV substantially improved the diagnostic accuracy for differentiating recurrent tumor and treatment from 86.8% to 92.3% for reader 1 and from 89.0% to 93.4% for reader 2, respectively. The intraclass correlation coefficients between readers were higher for perfusion parameters (intraclass correlation coefficient range, 0.84–0.89) than for diffusion parameters (intraclass correlation coefficient range, 0.68–0.79).CONCLUSIONS:Following gamma knife radiosurgery, intravoxel incoherent motion MR imaging can be used as a noninvasive imaging biomarker for differentiating recurrent tumor from treatment effect in patients with metastatic brain tumor.

Perfusion MR imaging techniques have significantly advanced and can now provide information regarding tumor physiology. There are several reports suggesting the usefulness of dynamic susceptibility contrast-enhanced perfusion MR imaging for differentiating recurrent metastatic brain tumor from stereotactic radiosurgery–induced radiation necrosis.^1–3 However, quantitative brain perfusion measurement remains a challenge for currently available MR perfusion methods. DSC and dynamic contrast-enhanced MR imaging are inhibited by their signal nonlinearity, and arterial spin-labeling exhibits, in addition to a low signal-to-noise ratio, a strong dependence on the transit time.Le Bihan et al⁴ defined intravoxel incoherent motion (IVIM) as the microscopic translational motion occurring in each image voxel in MR imaging. In biologic tissue, this incoherent motion includes molecular diffusion of water and microcirculation of blood in the capillary network, referred to as “perfusion.” These 2 phenomena account for the biexponential decay of the signal intensity on DWI when different diffusion b-values are applied. With the IVIM theory, both true molecular diffusion and water molecule motion in the capillary network can be estimated by using a single diffusion imaging-acquisition technique. As opposed to DSC, dynamic contrast-enhanced imaging, and arterial spin-labeling, IVIM has a unique capillary dependence that is not sensitive to the coherent laminar flow of arteries and veins. The measurement of IVIM is intrinsically local (ie, the encoding and readout are performed at the same location).⁵In our clinical experience, the major advantage of IVIM MR imaging is that because it allows the simultaneous acquisition of diffusion and perfusion parameters, it can provide both measures within corresponding solid lesions without the requirement for a further coregistration processing step. In the current study, we attempted to validate the IVIM-derived perfusion and diffusion parameters by using the clinicoradiologic correlation in patients with post-gamma knife radiosurgery (GKRS) metastatic brain tumor. We also assessed the diagnostic accuracy and added value of the IVIM method for differentiating recurrent tumor from treatment effect, compared with the combination of DSC perfusion MR imaging and DWI, which has commonly been used as a parameter for brain tumor imaging.Our hypothesis was that the difference in vascularity between recurrent tumor and the treatment effect can be assessed by using an IVIM-derived perfusion fraction (f); and the combination of f and the true diffusion parameter (D) would show diagnostic performance comparable with the combination of normalized CBV (nCBV) and the ADC. The purpose of this study was to determine the utility of IVIM-derived perfusion and diffusion parameters for assessing the treatment response of metastatic brain tumor following GKRS.     

Enhancing pancreatic adenocarcinoma delineation in diffusion derived intravoxel incoherent motion f‐maps through automatic vessel and duct segmentation

Diffusion‐based intravoxel incoherent motion imaging has recently gained interest as a method to detect and characterize pancreatic lesions, especially as it could provide a radiation‐ and contrast agent‐free alternative to existing diagnostic methods. However, tumor delineation on intravoxel incoherent motion‐derived parameter maps is impeded by poor lesion‐to‐pancreatic duct contrast in the f‐maps and poor lesion‐to‐vessel contrast in the D‐maps. The distribution of the diffusion and perfusion parameters within vessels, ducts, and tumors were extracted from a group of 42 patients with pancreatic adenocarcinoma. Clearly separable combinations of f and D were observed, and receiver operating characteristic analysis was used to determine the optimal cutoff values for an automated segmentation of vessels and ducts to improve lesion detection and delineation on the individual intravoxel incoherent motion‐derived maps. Receiver operating characteristic analysis identified f = 0.28 as the cutoff for vessels (Area under the curve (AUC) = 0.901) versus tumor/duct and D = 1.85 μm²/ms for separating duct from tumor tissue (AUC = 0.988). These values were incorporated in an automatic segmentation algorithm and then applied to 42 patients. This yielded clearly improved tumor delineation compared to individual intravoxel incoherent motion‐derived maps. Furthermore, previous findings that indicated that the f value in pancreatic cancer is strongly reduced compared to healthy pancreatic tissue were reconfirmed. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

定量MRI诊断直肠癌淋巴结转移的研究进展

评估直肠癌淋巴结转移对治疗和预后至关重要。常规MRI诊断直肠癌淋巴结转移主要依据淋巴结的短径和形态学特征,诊断效能较低。定量MRI包括动态增强MRI（DCE-MRI）、动态磁敏感增强MRI（DSC-MRI）、单指数模型扩散加权成像（DWI）、扩散峰度成像（DKI）、体素内不相干运动扩散加权成像（IVIM-DWI）等,可以对直肠癌淋巴结及原发灶进行定量分析,从而有助于诊断淋巴结转移。就常规MRI及定量MRI诊断直肠癌淋巴结转移的研究进展予以综述。     

Renal artery stenosis: in vivo perfusion MR imaging

The intravoxel incoherent motion (IVIM) model of perfusion and diffusion imaging was applied to an in vivo canine model of unilateral renal artery stenosis and was compared with relative renal blood flow determination with radioactive microspheres. The percentage relative renal blood flow as determined with radioactive microspheres correlated closely with the percentage apparent diffusion coefficient. If this method can be adapted to human imaging, it may provide a noninvasive means for detecting renal artery stenosis.     

Echo-planar imaging of intravoxel incoherent motion

The recently established single-shot technique of echo-planar imaging of intravoxel incoherent motion (IVIM) for determining and imaging the variations of microscopic motions of water has been applied to studies of water perfusion in phantoms and to in vivo studies of diffusion and perfusion in cat and human brains. The phantom results demonstrate that perfusion levels comparable with those found in vivo have easily observable and reproducible effects on signal amplitude that are consistent with previous IVIM theory. Reliable measurements of the diffusion coefficient in various types of brain tissue have been obtained. The results for white matter are consistent with the existence of anisotropic diffusion in oriented bundles of myelinated nerve fibers. The results for gray matter can be fitted to the IVIM theory and suggest a value of up to 14% for the fraction of the signal contributed by randomly perfusing fluid in normal cerebral cortex.     

单指数、双指数模型多b值DWI在胰腺癌的应用价值

目的 探讨单指数、体素内不相干运动成像(IVIM)双指数模型多b值扩散加权成像(DWI)定量参数在胰腺癌的应用价值.方法 应用3.0T磁共振扫描仪对临床或手术证实的37例胰腺癌患者行胰腺多b值DWI.应用单指数、IVIM双指数模型分析多b值DWI,测量胰腺癌和癌周胰腺组织的标准化表观扩散系数(ADCstandard)、纯扩散系数 (ADCslow)、假扩散系数(ADCfast) 和灌注分数(f),并应用独立样本t检验进行统计学分析.结果 胰腺癌的ADCslow值高于癌周胰腺组织的ADCslow值(0.611×10-3 mm2/s vs 0.521×10-3 mm2/s,P=0.037),而胰腺癌的ADCfast和f值低于癌周胰腺组织的ADCfast和f值(5.066×10-3 mm2/s vs 7.188×10-3 mm2/s,P=0.035;55.8% vs 64.0%,P=0.016),差异均有统计学意义.胰腺癌的ADCstandard值和ADCslow值显著正相关(r =0.824,P=0.000);ADCfast值和f值显著负相关(r=-0.558,P=0.000).结论 IVIM-DWI的灌注相关参数(ADCfast、f)和扩散相关参数(ADCslow)可以有效鉴别胰腺癌和癌周胰腺组织,IVIM-DWI是无创性早期诊断和鉴别胰腺癌与癌周胰腺组织的理想方法之一.     

Intravoxel incoherent motion MR imaging for prostate cancer: An evaluation of perfusion fraction and diffusion coefficient derived from different b‐value combinations

There has been a resurgent interest in intravoxel incoherent motion (IVIM) MR imaging to obtain perfusion as well as diffusion information on lesions, in which the diffusion was modeled as Gaussian diffusion. However, it was observed that this diffusion deviated from expected monoexponential decay at high b‐values and the reported perfusion in prostate is contrary to the findings in dynamic contrast‐enhanced (DCE) MRI studies and angiogenesis. Thus, this work is to evaluate the effect of different b‐values on IVIM perfusion fractions (f) and diffusion coefficients (D) for prostate cancer detection. The results show that both parameters depended heavily on the b‐values, and those derived without the highest b‐value correlated best with the results from DCE‐MRI studies; specifically, f was significantly elevated (7.2% vs. 3.7%) in tumors when compared with normal tissues, in accordance with the volume transfer constant (K^trans; 0.39 vs. 0.18 min^?1) and plasma fractional volume (v_p; 8.4% vs. 3.4%). In conclusion, it is critical to choose an appropriate range of b‐values in studies or include the non‐Gaussian diffusion contribution to obtain unbiased IVIM measurements. These measurements could eliminate the need for DCE‐MRI, which is especially relevant in patients who cannot receive intravenous gadolinium‐based contrast media. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Could intravoxel incoherent motion diffusion-weighted magnetic resonance imaging be feasible and beneficial to the evaluation of gastrointestinal tumors histopathology and the therapeutic response?

Gastrointestinal tumors (GTs) are among the most common tumors of the digestive system and are among the leading causes of cancer death worldwide. Functional magnetic resonance imaging (MRI) is crucial for assessment of histopathological changes and therapeutic responses of GTs before and after chemotherapy and radiotherapy. A new functional MRI technique, intravoxel incoherent motion (IVIM), could reveal more detailed useful information regarding many diseases. Currently, IVIM is widely used for various tumors because the derived parameters (diffusion coefficient, D; pseudo-perfusion diffusion coefficient, D*; and perfusion fraction, f) are thought to be important surrogate imaging biomarkers for gaining insights into tissue physiology. They can simultaneously reflect the microenvironment, microcirculation in the capillary network (perfusion) and diffusion in tumor tissues without contrast agent intravenous administration. The sensitivity and specificity of these parameters used in the evaluation of GTs vary, the results of IVIM in GTs are discrepant and the variability of IVIM measurements in response to chemotherapy and/or radiotherapy in these studies remains a source of controversy. Therefore, there are questions as to whether IVIM diffusion-weighted MRI is feasible and helpful in the evaluation of GTs, and whether it is worthy of expanded use.     

Magnetic resonance perfusion/diffusion imaging of the excised dog kidney.

RATIONALE AND OBJECTIVES. The authors developed a model of tissue capillary beds applicable to perfusion/diffusion imaging with magnetic resonance imaging (MRI). The model consists of a formalin-fixed excised dog kidney attached to a variable speed pump. With this system, it is possible to perfuse the kidney at selected rates. METHODS. Using the intravoxel incoherent motion model (IVIM), the apparent diffusion coefficient (ADC), diffusion coefficient (D), and perfusion fraction (f) were computed for a region of interest (ROI) in the renal cortex and in the medulla of seven kidneys, one of which was injected with a vasodilator before fixation. ADC and D values were computed for both cortex and medulla. These values were normalized to zero flow and plotted against renal perfusion. The perfusion fraction f was expressed in percent and was not normalized to zero flow. RESULTS. Normalized ADC and f were correlated with tissue perfusion rates using the Spearman rank-sum test (n = 18, rs greater than 0.5, P less than or equal to .02 for the standard preparation in both cortex and medulla), whereas normalized D (rs much less than 0.5) was uncorrelated for both preparations in cortex and medulla. CONCLUSIONS. The isolated perfused dog kidney is a useful model of tissue capillary beds for perfusion imaging technique development. The perfusion/diffusion-related parameters ADC and f increase as flow increases in the tissues, whereas D does not.     

腹部IVIM-DWI应用研究及进展

体素内不均一运动(IVIM)是指MR扩散加权成像(DWI)上体素内信号衰减同时包括真性水分子扩散和毛细血管网中随机血流微循环灌注,导致表观扩散系数(ADC)值反映的信息有限。采用多b值可获取系列DWI影像,根据双指数模型拟合,可同时获得组织的扩散和灌注信息,更全面地分析组织扩散成像数据。IVIM-DWI目前已广泛应用于肝脏、胰腺、肾脏、前列腺等脏器,就该技术在腹部MR成像中的应用研究现状及进展予以综述。     

Updates in advanced diffusion-weighted magnetic resonance imaging techniques in the evaluation of prostate cancer

Diffusion-weighted magnetic resonance imaging (DW-MRI) is considered part of the standard imaging protocol for the evaluation of patients with prostate cancer. It has been proven valuable as a functional tool for qualitative and quantitative analysis of prostate cancer beyond anatomical MRI sequences such as T2-weighted imaging. This review discusses ongoing controversies in DW-MRI acquisition, including the optimal number of b-values to be used for prostate DWI, and summarizes the current literature on the use of advanced DW-MRI techniques. These include intravoxel incoherent motion imaging, which better accounts for the non-mono-exponential behavior of the apparent diffusion coefficient as a function of b-value and the influence of perfusion at low b-values. Another technique is diffusion kurtosis imaging (DKI). Metrics from DKI reflect excess kurtosis of tissues, representing its deviation from Gaussian diffusion behavior. Preliminary results suggest that DKI findings may have more value than findings from conventional DW-MRI for the assessment of prostate cancer.     

Diffusion-weighted imaging of pancreatic cancer

Magnetic resonance imaging (MRI) is a reliable and accurate imaging method for the evaluation of patients with pancreatic ductal adenocarcinoma (PDAC). Diffusion-weighted imaging (DWI) is a relatively recent technological improvement that expanded MRI capabilities, having brought functional aspects into conventional morphologic MRI evaluation. DWI can depict the random diffusion of water molecules within tissues (the so-called Brownian motions). Modifications of water diffusion induced by different factors acting on the extracellular and intracellular spaces, as increased cell density, edema, fibrosis, or altered functionality of cell membranes, can be detected using this MR sequence. The intravoxel incoherent motion (IVIM) model is an advanced DWI technique that consent a separate quantitative evaluation of all the microscopic random motions that contribute to DWI, which are essentially represented by molecular diffusion and blood microcirculation (perfusion). Technological improvements have made possible the routine use of DWI during abdominal MRI study. Several authors have reported that the addition of DWI sequence can be of value for the evaluation of patients with PDAC, especially improving the staging; nevertheless, it is still unclear whether and how DWI could be helpful for identification, characterization, prognostic stratification and follow-up during treatment. The aim of this paper is to review up-to-date literature data regarding the applications of DWI and IVIM to PDACs.     

DCE-MRI及IVIM-DWI在头颈部恶性肿瘤 诊疗中的研究进展

动态增强磁共振成像（DCE-MRI）及体素内不相干运动扩散加权成像（IVIM-DWI）通过定量描述组织内血流灌注、水分子扩散等信息，能够先于形态学改变反映组织生理、病理状态变化。近年来，DCE-MRI及IVIM-DWI单独或联合应用在头颈部恶性肿瘤（HNC）鉴别诊断、早期疗效评估、预后预测、残留或复发判定、唾液腺功能放射性损伤监测等方面均展现出一定的临床应用潜力。就DCE-MRI及IVIM-DWI在HNC诊疗方面的应用研究进展予以综述。     

Magnetic resonance: perfusion and diffusion imaging

Summary The use of magnetic resonance imaging to detect normal and pathological problems of perfusion and diffusion is reviewed. Motion sensitised spin-echo images can be used to detect changes in slow flow velocity within a voxel (intravoxel coherent motion (IVCM) as well as intravoxel incoherent motion (IVIM) effects attributable to both diffusion and perfusion. Changes have been identified in a variety of brain diseases in the absence of changes in conventional images but the techniques are very vulnerable to motion artefact of all types. More rapid and more sensitive approaches using steady state free precision and echo-planer imaging are being investigated. Anisotropic diffusion imaging enables white matter tracts to be demonstrated within the brain and spinal cord as a function of their direction because diffusion of water across axons is much more restricted than it is along them. This technique provides a unique method for localisation of lesions and displays obvious changes in disease in which diffusion becomes less restricted.