On the identifiability of pharmacokinetic parameters in dynamic contrast-enhanced imaging.

The so-called "Kety model" is a two-compartment pharmacokinetic model describing tumor perfusion kinetics. Its parameters, the transendothelial transfer constant (K(trans)), extravascular extracellular volume fraction (upsilon(e)), and microvascular plasma volume fraction (upsilon(p)), can be estimated with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). However, the results obtained by current methods show large variation in predictability and reliability. Here, the aim was to examine which experimental conditions have to be fulfilled to avoid large uncertainties and mutual dependencies of the parameters. Using frequency response analysis and simulation, the identifiability of the model was examined. The requirements and influence of contrast enhancement measurements, such as temporal resolution, signal to noise ratio, and contrast injection rate, on the accuracy of the parameters were analyzed. Tissue response characteristics revealed a low-frequency system with a cutoff frequency equal to K(trans)/upsilon(e), which confines the required temporal resolution. For malignant tissue with hyperpermeable vasculature (high K(trans)) a higher sampling frequency is required to accurately estimate K(trans) than for normal tissue. Too low sampling rates or too low injection rates resulted in inaccurate K(trans) values and hereby unreliable classification of malignant tissue.     

Monitoring ankylosing spondylitis therapy by dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging

Objective The effects of different therapies on enthesitis/osteitis in active ankylosing spondylitis (AS) were evaluated by magnetic resonance imaging (MRI). The aim was to assess the role of quantitative MRI in the evaluation of AS treatment efficacy. Materials and methods Thirty patients with active spondylitis or bilateral sacroilitis were selected and followed up for 1 year. Ten of the patients were treated only with non-steroidal anti-inflammatory drugs, 10 patients additionally received at baseline an intravenous pulse of glucocorticoids and 10 patients were treated with regular infusions of infliximab. Disease activity was measured according to clinical instruments and laboratory tests. For each patient, one selected inflamed lesion was followed from baseline through control visits quantitatively by diffusion-weighted imaging (DWI) measuring the apparent diffusion coefficient (ADC) and by dynamic contrast-enhanced imaging (DCEI) with evaluation of the enhancement factor (f_enh) and enhancement gradient (g_enh). Results Clinical and quantitative MRI parameters diminished significantly with regression of the inflammatory activity. The improvement in AS was most pronounced in patients treated with infliximab; after 12 months the ADC diminished from an average of 1.31 to 0.88 × 10⁻³ mm²/s, f_enh from 1.85 to 0.60, and g_enh from 3.09 to 1.40 %/s. Conclusion Diffusion-weighted imaging and DCEI were shown to be effective in quantifying changes in inflammation in skeletal lesions during the treatment of AS, and could therefore be convenient for assessing treatment efficacy. To the best of our knowledge this is the first time DWI was used to evaluate the activity of skeletal inflammation in rheumatic diseases such as AS.     

Neoadjuvant chemotherapy in breast cancer-response evaluation and prediction of response to treatment using dynamic contrast-enhanced and diffusion-weighted MR imaging

Objective  

To explore the predictive value of MRI parameters and tumour characteristics before neoadjuvant chemotherapy (NAC) and to compare changes in tumour size and tumour apparent diffusion coefficient (ADC) during treatment, between patients who achieved pathological complete response (pCR) and those who did not.     

应用对比剂动态增强和扩散加权MRI进行乳腺癌新辅助化疗疗效的评价和预测

目的探讨在接受新辅助化疗(neoadjuvant chemotherapy,NAC)后获得病理上完全缓解(pathological complete response,pCR)和不能缓解的病人之间,化疗之前MRI参数和肿瘤特征的预测价值,并比较在治疗过程中肿瘤大小和表观扩散系数的改变。方法     

Assessment of early therapeutic response to sorafenib in renal cell carcinoma xenografts by dynamic contrast-enhanced and diffusion-weighted MR imaging

Objective:

To investigate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DWI) in monitoring early therapeutic response to sorafenib in renal cell carcinoma (RCC) xenograft models.

Methods:

Sorafenib (40 mg kg⁻¹) was administered orally to BALB/c nude mice (n = 9) bearing subcutaneous tumours of human RCC ACHN xenografts. DCE-MRI and DWI were obtained 0, 1, 3 and 7 days after therapy, and DCE-MRI parameters (K^trans and v_e) and apparent diffusion coefficient (ADC) values were calculated. Tumour size and volume changes were correlated with changes in DCE-MRI parameters or ADC values after therapy.

Results:

Following therapy, K^trans showed a significant decrease over time (p = 0.005), whereas v_e did not demonstrate significant changes between time points (p = 0.97). ADC values showed a progressive increase over time (p = 0.004). Compared with pre-therapy, K^trans showed a significant decrease after 3 days of therapy (p = 0.039), and ADC values increased significantly after 7 days (p = 0.039). Tumour size and volume did not show significant changes during 7 days. Tumour size and volume changes were not associated with changes in DCE-MRI parameters or ADC values.

Conclusion:

DCE-MRI and DWI may show early physiological changes within 1 week after initiating sorafenib treatment on human RCC xenografts.

Advances in knowledge:

The quantitative parameters of DCE-MRI and DWI may offer the potential for assessing early therapeutic response to sorafenib in clinical trials.     

非小细胞肺癌:MR动态对比增强与扩散加权成像检测肺癌对化疗的早期反应

目的评估MR动态对比增强成像和扩散加权成像检测非小细胞肺癌(NSCLC)病人对化疗早期反应的能力。材料与方法本研究经机构审查委员会审批并获得受试者书面     

磁共振DWI及动态增强扫描在前列腺疾病诊断中的价值

目的探讨磁共振扩散加权成像(DWI)和动态增强扫描(DCE-MRI)在前列腺疾病中的诊断价值。方法经穿刺活检或手术病理证实的20例前列腺癌及31例前列腺增生(BPH)患者进行了MR常规扫描、DWI和DCE-MRI扫描,测量病变的表观扩散系数(ADC)值,观察病灶常规MRI、DWI和动态增强MRI特征,绘制信号强度-时间曲线(SI-T曲线),SI-T曲线分成3型:Ⅰ型为信号强度早期增高后仍持续增高;Ⅱ型为信号强度早期增高后出现平台期;Ⅲ型为信号强度早期增高后出现下降期。经方差分析比较不同组织和病灶间差异。结果经DCE-MRI检查,20例前列腺癌患者中17例病灶区呈Ⅲ型曲线,2例呈Ⅱ型曲线,1例呈Ⅰ型曲线;31例前列腺增生患者中26例呈Ⅰ型曲线,4例呈Ⅱ型曲线,1例呈Ⅲ型曲线。前列腺癌组与BPH组的SI-T曲线类型分布的差异有统计学意义(P<0.01)。20例前列腺癌病灶于DWI上为高信号,于ADC图上呈明显低信号,ADC值为(1.18±0.08)×10-3 mm2/s,未被癌组织侵及的外围叶于DWI、ADC图上均呈等信号,ADC值为(2.67±0.09)×10-3 mm2/s;31例前列腺增生患者中央叶和外围叶于DWI、ADC图上均呈等信号,ADC值分别为(1.87±0.07)×10-3 mm2/s、(2.64±0.11)×10-3mm2/s。除前列腺增生的外围叶与未被癌组织侵及的外围叶之间差异无统计学意义(P>0.05)外,前列腺增生、前列腺癌、前列腺增生的外围叶和未被癌组织侵及的外围叶各组之间差异均有统计学意义(P<0.05)。DCE-MRI和DWI联合应用在前列腺癌诊断的敏感度、特异度和准确度均达80%以上。结论 DCE-MRI、DWI在前列腺癌和前列腺增生中具有特征性影像学表现,2种方法联合应用提高了MRI诊断前列腺癌的诊断和分期准确率。     

Accurate estimation of pharmacokinetic contrast-enhanced dynamic MRI parameters of the prostate

Quantitative analysis of contrast-enhanced dynamic MR images has potential for diagnosing prostate cancer. Contemporary fast acquisition techniques can give sufficiently high temporal resolution to sample the fast dynamics observed in the prostate. Data reduction for parametric visualization requires automatic curve fitting to a pharmacokinetic model, which to date has been performed using least-squares error minimization methods. We observed that these methods often produce unexpectedly noisy estimates, especially for the typically fast, intermediate parameters time-to-peak and start-of-enhancement, resulting in inaccurate pharmacokinetic parameter estimates. We developed a new curve fit method that focuses on the most probable slope. A set of 10 patients annotated using histopathology was used to compare the conventional and new methods. The results show that our new method is significantly more accurate, especially in the relatively less-enhancing peripheral zone. We conclude that estimation accuracy depends on the curve fit method, which is especially important when evaluating the peripheral zone of the prostate.     

Combined diffusion-weighted and dynamic contrast-enhanced imaging of patients with acute osteoporotic vertebral fractures

Objectives

To evaluate the potential and to analyze parameter correlations of combined quantitative diffusion-weighted MRI (DWI) and high-temporal-resolution dynamic contrast-enhanced MRI (DCE-MRI) in vertebral bone marrow (vBM) of patients with osteoporosis and acute vertebral compression fractures, providing additional information for a better understanding of the physiological background of parameter changes.

Materials and methods

20 patients with acute osteoporotic fractures were examined with DWI and DCE-MRI at 1.5 T. DCE-MRI was performed with a 2D saturation-recovery turbo-FLASH sequence, acquiring 300 dynamics with a temporal resolution of 1 s. For DWI measurements, a DW HASTE sequence with b-values from 100 to 600 s/mm² was applied. In each patient, ROIs were drawn manually in the fractures and in normal appearing vertebrae. For DCE-MRI, the concentration-time curves of these ROIs were analyzed using a two-compartment tracer-kinetic model in the lesions, providing separate estimates of perfusion and permeability, and a one-compartment model in normal vBM, providing only a mixed representation of perfusion and permeability in terms of a mixed flow parameter K^trans and the extracellular volume (ECV). In the case of DWI, attenuation curves were fitted to a monoexponential decay model to determine the apparent diffusion coefficient (ADC).

Results

Mean perfusion parameters and ADCs were significantly (p < 0.001) different in the fractures compared to adjacent normal appearing vertebrae (K^trans: 7.81 mL/100 mL/min vs. 14.61 mL/100 mL/min, ECV: 52.84 mL/100 mL vs. 4.61 mL/100 mL, ADC: 1.71 × 10^-3 mm²/s vs. 0.57 × 10^-3 mm²/s). ADCs showed a significant correlation with the ECV.

Conclusion

The quantitative analysis of DWI and DCE-MRI could distinguish osteoporotic fractures from normal appearing vertebrae. A significant correlation found between ECV and ADCs might be able to explain the cause for the increased diffusivity in osteoporotic fractures. Since the other perfusion parameters do not correlate with the ADC, they provide additional pathophysiological information not accessible with DWI.     

Evaluation of the modified Van Assche index for assessing response to anti-TNF therapy with MRI in perianal fistulizing Crohn's disease

BackgroundStructured evaluation of magnetic resonance imaging (MRI) is important to guide clinical decisions of perianal fistulas in Crohn's disease (CD) patients.PurposeTo evaluate the recently developed modified Van Assche index to assess clinical responses to anti-tumor necrosis factor (TNF) therapy in patients with perianal fistulizing CD.MethodsA search of medical records identified patients with fistulizing perianal CD who underwent baseline and follow-up MRI while receiving anti-TNF treatment. Patients were divided into clinical responders and non-responders based on physician's assessment. MRI-scans were scored using the original and modified Van Assche index and scores between baseline and follow-up were compared within clinical responders and non-responders.ResultsThirty cases were included (48% female, median age 27 years). Clinical responders (n = 16) had a median modified Van Assche score of 9.6 (IQR 5.8–12.7) at baseline and 5.8 (IQR 3.5–8.5) at follow-up (p = 0.008). In non-responders (n = 14), corresponding scores were 7.7 (IQR 5.8–13.5) and 8.2 (IQR 5.8–11.5) (p = 0.624). In clinical responders, 6/16 showed no drop in modified Van Assche score at follow-up. Scores obtained with the original Van Assche index dropped between baseline and follow-up in clinical responders (13.0 vs. 9.6, p = 0.011), whereas no decrease was observed in non-responders (11.5 vs. 11.5, p = 0.324).ConclusionsWhile the modified Van Assche index overall decreases significantly in patients with perianal fistulas responding to anti-TNF treatment, one third of responders had unaltered scores at follow-up. Also, outcomes were comparable to the original Van Assche index. Further optimization of the modified Van Assche index is needed before application in larger studies.     

Changes underlying the dynamic contrast-enhanced MRI response to treatment in rheumatoid arthritis

Objective Dynamic contrast-enhanced MRI of patients with rheumatoid arthritis has shown a decrease in the early enhancement rate (EER) of synovitis after treatment. The purpose of this work was to investigate the underlying changes. Methods 3D dynamic contrast-enhanced images were acquired from 13 patients before and 1–2 weeks after anti-TNFα treatment. The EER of the inflamed synovium was measured. The T₁ relaxation time of the synovitis was calculated from images at different flip angles. The time course of the arrival of gadolinium at the radial artery was determined. The gadolinium enhancement of the inflamed synovium was modeled to calculate the fractional plasma volume (v_p), the fractional extravascular, extracellular fluid volume (v_e), and the volume transfer constant (K^trans). Pre- and post-treatment values were compared and the dependence of the EER on each parameter was assessed. Results There was a decrease in the EER measured over 26 s after treatment (29%, p = 0.002). Reductions in T₁ (12%, p = 0.001), K^trans (31%, p = 0.002), and v_p (43%, p = 0.01) contributed to this; however, the EER was relatively insensitive to changes in v_e. Conclusions The decrease in EER after anti-TNFα treatment is largely caused by reductions in the volume transfer constant K^trans, the fractional plasma volume v_p, and the T₁ relaxation time. Only the contributions from K^trans and v_p directly reflect synovial vascularity.     

DCE-MRI联合DWI诊断小肝癌的临床价值

目的 分析3.0T DCE-MRI联合DWI在小肝癌(SHCC)诊断和鉴别诊断中的价值.方法 回顾性分析59例经手术或穿刺活检病理证实的68个SHCC的3.0T MRI容积采集技术(LAVA),多期Gd-DTPA动态增强和弥散(DWI)影像特点.结果 SHCC在Gd-DTPA动态强化及DWI的影像学表现.68个SHCC病灶中,94.1％(64/68)在DWI呈高信号,ADC呈低信号;5.9％(4/68)肝硬化背景明显者呈略高信号,ADC图呈略低信号.平扫T1WI86.8％(59/68)病灶表现为低信号,8.8％(6/68)表现为等信号,4.4％(3/68)表现为高信号.Gd-DTPA动态强化,75％(51/68)病灶动脉期呈高信号、门脉期及平衡期呈低信号,8.8％(6/68)病灶动脉期及门脉期呈高信号、平衡期呈低信号,11.8％ (8/68)病灶动脉期强化呈稍高信号、门脉期及平衡期呈等信号,4.4％(3/68)病灶动脉期及门脉期呈无强化等信号、平衡期呈稍低信号.结论 小肝癌在DWI(b=500)上表现为高信号,绝大多数小肝癌在MR动态增强图像上表现为动脉期明显强化.因此,联合DWI和DCE-MRI明显有助于提高小肝癌的诊断和鉴别诊断.     

Intravoxel incoherent motion diffusion-weighted MR imaging in differentiation of lung cancer from obstructive lung consolidation: comparison and correlation with pharmacokinetic analysis from dynamic contrast-enhanced MR imaging

Objectives

To test whether parameters derived from intravoxel incoherent motion (IVIM) can be used to distinguish lung cancer from obstructive pulmonary consolidation by comparing them with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-derived parameters and to evaluate the correlation between these quantitative parameters.

Methods

A total of 31 lung cancer patients, confirmed by pathology and obstructive consolidations confirmed by positron emission tomography/computed tomography (PET-CT), were recruited. All of them were assessed with structural MRI and IVIM and 17 of them underwent additional DCE-MRI examinations. Parameters derived from IVIM and DCE-MRI in the tumour and consolidation were analysed, and the optimal cut-off values in differential diagnosis were obtained.

Results

ADC_total, D and f values were lower (P?<?0.05), while IAUC₆₀ was higher in lung cancers (P?=?0.013) compared with obstructive pulmonary consolidations. According to the ROC curve, ADC_total outperformed other perfusion and diffusion parameters with the optimal cut-off value of 1.409?×?10^-3 mm²/s (AUC?=?0.95). Poor correlations were found between parameters derived from IVIM and DCE-MRI.

Conclusions

IVIM-MRI is potentially useful in the differentiation of lung cancer and obstructive pulmonary consolidation. ADC_total, D and f may be reliable independent discriminating markers, but D ^* is variable with low diagnostic accuracy.

Key Points

? Lung cancer and consolidation differentiation is essential for treatment decision-making. ? Perfusion and diffusion characteristics of lesions could help differential diagnosis. ? IVIM can separate reflection of tissue diffusivity and microcapillary perfusion. ? The relationship between perfusion quantified by IVIM and DCE-MRI is controversial.     

Added value of diffusion-weighted MR imaging to T2-weighted and dynamic contrast-enhanced MR imaging in T staging of gastric cancer

ObjectiveTo assess the utilization of diffusion-weighted (DW) magnetic resonance (MR) imaging in T staging of gastric cancer prospectively.MethodsFifty-one patients underwent T2-weighted (T2W), contrast-enhanced (CE) and DW MR imaging. Two radiologists independently interpreted the images for T staging of the tumors.ResultsThe overall accuracy of T staging in pT1-4 gastric cancers by T2W+CE+DW (88.2%) was significantly higher than that by T2W+CE and T2W+DW (both 76.5%, P= .031).ConclusionDW adds useful information to T2W and CE MR imaging in T staging of gastric cancer.     

Non-mass-like enhancement on contrast-enhanced breast MR imaging: Lesion characterization using combination of dynamic contrast-enhanced and diffusion-weighted MR images

Purpose

To evaluate the diagnostic accuracy of a combination of dynamic contrast-enhanced MR imaging (DCE-MRI) and diffusion-weighted MR imaging (DWI) in characterization of lesions showing non-mass-like enhancement on breast MR imaging and to find the strongest discriminators between carcinoma and benignancy.

Materials and methods

We analyzed consecutive MR images in 45 lesions showing non-mass like enhancement in 41 patients. We analyzed lesion size, distribution, internal enhancement, kinetic curve pattern, and apparent diffusion coefficient (ADC) values. We applied univariate and multivariate analyses to find the strongest indicators for malignancy. In a validation study, 22 non-mass-like enhancement lesions in 21 patients were examined. We calculated diagnostic accuracy when we presume category 4b, 4c, and 5 lesions as malignant or high to moderate suspicion for malignancy, and category 4a and 3 as low suspicion for malignancy or benign.

Results

Segmental distribution (P = 0.018), clumped internal enhancement (P = 0.005), and ADC less than 1.3 × 10⁻³ mm²/s (P = 0.047) were the strongest MR indicators of malignancy. In a validation study, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 87% (13/15), 86% (6/7), 93% (13/14), 75% (6/8) and 86% (19/22), respectively.

Conclusion

The combination of DCE-MRI and DWI showed high diagnostic accuracy in characterization of non-mass-like enhancement lesions on breast MR images.