Hypo-Vascular Liver Metastases Treated with Transarterial chemoembolization: Assessment of Early Response by Volumetric Contrast-Enhanced and Diffusion-Weighted Magnetic Resonance Imaging

OBJECTIVE: To evaluate the value of anatomic and volumetric functional magnetic resonance imaging (MRI) in early assessment of response to trans-arterial chemoembolization (TACE) in hypovascular liver metastases. METHODS: This retrospective study included 52 metastatic lesions (42 targeted and 10 non-targeted) in 17 patients who underwent MRI before and early after TACE. Two reviewers reported response by anatomic criteria (Response Evaluation Criteria in Solid Tumor [RECIST], modified RECIST [mRECIST], and European Association for the Study of Liver Disease [EASL]) and functional criteria (volumetric apparent diffusion coefficient and contrast enhancement). Treatment endpoint was RECIST at 6 months. A 2-sample paired t test was used to compare the mean changes after intra-arterial therapy. P < .05 was considered statistically significant. RESULTS: Reduction in mRECIST and EASL at 1 month was significant in the whole cohort as well as in responders by RECIST at 6 months, and the changes fulfilled partial response criteria for both metrics in responders. Responders also had significant changes in volumetric apparent diffusion coefficient (P = .01 and P = .03) and contrast enhancement (P < .0001 and P < .0001) at 1 month for both readers, respectively. CONCLUSION: At 1 month post treatment, responders did not fulfill RECIST criteria but fulfilled mRECIST and EASL criteria. In addition, volumetric contrast-enhanced and diffusion-weighted MRI may be helpful in evaluating early treatment response after TACE in hypovascular liver metastases in patients who have failed to respond to initial chemotherapy.     

Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Gd-EOB-DTPA for the Evaluation of Liver Fibrosis Induced by Carbon Tetrachloride in Rats

Purpose

To investigate the utility of dynamic contrast-enhanced MRI (DCE-MRI) with Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for detecting liver fibrosis induced by carbon tetrachloride (CCl₄) in rats.

Methods

This study was approved by the institutional animal care and use committee. Liver fibrosis in rats was induced by intraperitoneal injection of 1 mL/kg 50% CCl₄ twice a week for 4-13 weeks. Control rats were injected with saline. Liver fibrosis was graded using the Metaviar score: no fibrosis (F0), mild fibrosis (F1-F2) and advanced fibrosis (F3-F4). DCE-MRI with Gd-EOB-DTPA was performed for all rats. K^trans, K_ep, V_e and iAUC of the liver parenchyma were measured. Relative enhancement (RE) value of the liver was calculated on T₁-weighted images at 15, 20 and 25 min after Gd-EOB-DTPA administration.

Results

Thirty-five rats were included: no fibrosis (n=13), mild fibrosis (n=11) and advanced fibrosis (n=11). K^trans and iAUC values were highest in advanced fibrosis group and lowest in no fibrosis group (P＜0.05). The area under the receiver operating characteristic curve (AUROC) for fibrosis (stages F1 and greater) were 0.773 and 0.882 for K^trans and iAUC, respectively. AUROC for advanced fibrosis were 0.835 and 0.867 for K^trans and iAUC, respectively. K_ep and RE values were not able to differentiate fibrosis stages (all P＞0.05).

Conclusion

K^trans and iAUC obtained from DCE-MRI with Gd-EOB-DTPA are useful for the detection and staging of rat liver fibrosis induced by CCl₄.     

Spleen Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a New Method for Staging Liver Fibrosis in a Piglet Model

Objective

To explore spleen hemodynamic alteration in liver fibrosis with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and to determine how to stage liver fibrosis with spleen DCE-MRI parameters.

Materials and Methods

Sixteen piglets were prospectively used to model liver fibrosis staged by liver biopsy, and underwent spleen DCE-MRI on 0, 5th, 9th, 16th and 21st weekend after modeling this disease. DCE-MRI parameters including time to peak (TTP), positive enhancement integral (PEI), maximum slope of increase (MSI) and maximum slope of decrease (MSD) of spleen were measured, and statistically analyzed to stage this disease.

Results

Spearman''s rank correlation tests showed that TTP tended to increase with increasing stages of liver fibrosis (r = 0.647, P<0.001), and that PEI tended to decrease from stage 0 to 4 (r = −0.709, P<0.001). MSD increased slightly from stage 0 to 2 (P>0.05), and decreased from stage 2 to 4 (P<0.05). MSI increased from stage 0 to 1, and decreased from stage 1 to 4 (all P>0.05). Mann-Whitney tests demonstrated that TTP and PEI could classify fibrosis between stage 0 and 1–4, between 0–1 and 2–4, between 0–2 and 3–4, or between 0–3 and 4 (all P<0.01). MSD could discriminate between 0–2 and 3–4 (P = 0.006), or between 0–3 and 4 (P = 0.012). MSI could not differentiate between any two stages. Receiver operating characteristic analysis illustrated that area under receiver operating characteristic curve (AUC) of TTP was larger than of PEI for classifying stage ≥1 and ≥2 (AUC = 0.851 and 0.783, respectively). PEI could best classify stage ≥3 and 4 (AUC = 0.903 and 0.96, respectively).

Conclusion

Spleen DCE-MRI has potential to monitor spleen hemodynamic alteration and classify liver fibrosis stages.     

Noninvasive Identification of Viable Cell Populations in Docetaxel-Treated Breast Tumors Using Ferritin-Based Magnetic Resonance Imaging

Background

Cancer stem cells (CSCs) are highly tumorigenic and are responsible for tumor progression and chemoresistance. Noninvasive imaging methods for the visualization of CSC populations within tumors in vivo will have a considerable impact on the development of new CSC-targeting therapeutics.

Methodology/Principal Findings

In this study, human breast cancer stem cells (BCSCs) transduced with dual reporter genes (human ferritin heavy chain [FTH] and enhanced green fluorescence protein [EGFP]) were transplanted into NOD/SCID mice to allow noninvasive tracking of BCSC-derived populations. No changes in the properties of the BCSCs were observed due to ferritin overexpression. Magnetic resonance imaging (MRI) revealed significantly different signal intensities (R₂* values) between BCSCs and FTH-BCSCs in vitro and in vivo. In addition, distinct populations of pixels with high R₂* values were detected in docetaxel-treated FTH-BCSC tumors compared with control tumors, even before the tumor sizes changed. Histological analysis revealed that areas showing high R₂* values in docetaxel-treated FTH-BCSC tumors by MRI contained EGFP+/FTH+ viable cell populations with high percentages of CD44+/CD24− cells.

Conclusions/Significance

These findings suggest that ferritin-based MRI, which provides high spatial resolution and tissue contrast, can be used as a reliable method to identify viable cell populations derived from BCSCs after chemotherapy and may serve as a new tool to monitor the efficacy of CSC-targeting therapies in vivo.     

Radiology: Magnetic Resonance Imaging of Musculoskeletal Tumors

The Scientific Board of the California Medical Association presents the following inventory of items of progress in radiology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in radiology that have recently achieved a substantial degree of authoritative acceptance. Whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Radiology of the California Medical Association, and the summaries were prepared under its direction.     

Variations of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Evaluation of Breast Cancer Therapy Response: A Multicenter Data Analysis Challenge

Pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) time-course data allows estimation of quantitative parameters such as K^trans (rate constant for plasma/interstitium contrast agent transfer), v_e (extravascular extracellular volume fraction), and v_p (plasma volume fraction). A plethora of factors in DCE-MRI data acquisition and analysis can affect accuracy and precision of these parameters and, consequently, the utility of quantitative DCE-MRI for assessing therapy response. In this multicenter data analysis challenge, DCE-MRI data acquired at one center from 10 patients with breast cancer before and after the first cycle of neoadjuvant chemotherapy were shared and processed with 12 software tools based on the Tofts model (TM), extended TM, and Shutter-Speed model. Inputs of tumor region of interest definition, pre-contrast T₁, and arterial input function were controlled to focus on the variations in parameter value and response prediction capability caused by differences in models and associated algorithms. Considerable parameter variations were observed with the within-subject coefficient of variation (wCV) values for K^trans and v_p being as high as 0.59 and 0.82, respectively. Parameter agreement improved when only algorithms based on the same model were compared, e.g., the K^trans intraclass correlation coefficient increased to as high as 0.84. Agreement in parameter percentage change was much better than that in absolute parameter value, e.g., the pairwise concordance correlation coefficient improved from 0.047 (for K^trans) to 0.92 (for K^trans percentage change) in comparing two TM algorithms. Nearly all algorithms provided good to excellent (univariate logistic regression c-statistic value ranging from 0.8 to 1.0) early prediction of therapy response using the metrics of mean tumor K^trans and k_ep (= K^trans/v_e, intravasation rate constant) after the first therapy cycle and the corresponding percentage changes. The results suggest that the interalgorithm parameter variations are largely systematic, which are not likely to significantly affect the utility of DCE-MRI for assessment of therapy response.     

Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Prostate Cancer Clinical Trials: Potential Roles and Possible Pitfalls

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) evaluates the tissue microvasculature and may have a role in assessing and predicting therapeutic response in prostate cancer (PCa). In this review, we review principles of DCE-MRI and present the potential quantitative information that can be obtained. We discuss how it may be used as a biomarker for treatment with antiangiogenic and antivascular agents and potentially identify patients with PCa who may benefit from this form of therapy. Likewise, DCE-MRI may play a role in assessing response to combined androgen deprivation therapy and radiation therapy and theoretically could be a prognostic biomarker in evaluating second-generation hormone therapies. We also address the challenges of using DCE-MRI in PCa clinical trials and discuss the difficulties with standardization of this methodology to allow for biomarker validation, with particular reference to PCa.     

Functional Dynamic Contrast-Enhanced Magnetic Resonance Imaging in an Animal Model of Brain Metastases: A Pilot Study

Background

Brain metastasis is a common disease with a poor prognosis. The purpose of this study is to test feasibility and safety of the animal models for brain metastases and to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to enhance detection of brain metastases.

Methods

With approval from the institutional animal ethics committee, 18 New Zealand rabbits were randomly divided into three groups: Group A received an intra-carotid infusion (ICI) of mannitol followed by VX2 cells; group B received successive ICI of mannitol and heparin followed by VX2 cells; and group C received an ICI of normal saline. The survival rate and clinical symptoms were recorded after inoculation. After two weeks, conventional MRI and DCE-MRI were performed using 3.0 Tesla scanner. The number of tumors and detection rate were analyzed. After MRI measurements, the tumors were stained with hematoxylin-eosin.

Results

No rabbits died during the procedure. The rabbits had common symptoms, including loss of appetite, lassitude and lethargy, etc. at 10.8±1.8 days and 8.4±1.5 days post-inoculation in group A and B, respectively. Each animal in groups A and B re-gained the lost weight within 14 days. Brain metastases could be detected by MRI at 14 days post-inoculation in both groups A and B, with metastases manifesting as nodules in the brain parenchyma and thickening in the meninges. DCE-MRI increased the total detection of tumors compared to non-contrast MRI (P<0.05). The detection rates of T1-weighted image, T2-weighted image and DCE-MRI were 12%, 32% and 100%, respectively (P<0.05). Necropsy revealed nodules or thickening meninges in the gross samples and VX2 tumor cytomorphologic features in the slides, which were consistent with the MRI results.

Conclusions

The VX2 rabbit model of brain metastases is feasible, as verified by MRI and pathologic findings, and may be a suitable platform for future studies of brain metastases. Functional DCE-MRI can be used to evaluate brain metastases in a rabbit model.     

Pitfalls and Limitations of Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Urinary Bladder Cancer

Adequately selecting a therapeutic approach for bladder cancer depends on accurate grading and staging. Substantial inaccuracy of clinical staging with bimanual examination, cystoscopy, and transurethral resection of bladder tumor has facilitated the increasing utility of magnetic resonance imaging to evaluate bladder cancer. Diffusion-weighted imaging (DWI) is a noninvasive functional magnetic resonance imaging technique. The high tissue contrast between cancers and surrounding tissues on DWI is derived from the difference of water molecules motion. DWI is potentially a useful tool for the detection, characterization, and staging of bladder cancers; it can also monitor posttreatment response and provide information on predicting tumor biophysical behaviors. Despite advancements in DWI techniques and the use of quantitative analysis to evaluate the apparent diffusion coefficient values, there are some inherent limitations in DWI interpretation related to relatively poor spatial resolution, lack of cancer specificity, and lack of standardized image acquisition protocols and data analysis procedures that restrict the application of DWI and reproducibility of apparent diffusion coefficient values. In addition, inadequate bladder distension, artifacts, thinness of bladder wall, cancerous mimickers of normal bladder wall and benign lesions, and variations in the manifestation of bladder cancer may interfere with diagnosis and monitoring of treatment. Recognition of these pitfalls and limitations can minimize their impact on image interpretation, and carefully applying the analyzed results and combining with pathologic grading and staging to clinical practice can contribute to the selection of an adequate treatment method to improve patient care.     

Comparison of Optical and Power Doppler Ultrasound Imaging for Non-Invasive Evaluation of Arsenic Trioxide as a Vascular Disrupting Agent in Tumors

Small animal imaging provides diverse methods for evaluating tumor growth and acute response to therapy. This study compared the utility of non-invasive optical and ultrasound imaging to monitor growth of three diverse human tumor xenografts (brain U87-luc-mCherry, mammary MCF7-luc-mCherry, and prostate PC3-luc) growing in nude mice. Bioluminescence imaging (BLI), fluorescence imaging (FLI), and Power Doppler ultrasound (PD US) were then applied to examine acute vascular disruption following administration of arsenic trioxide (ATO).During initial tumor growth, strong correlations were found between manual caliper measured tumor volume and FLI intensity, BLI intensity following luciferin injection, and traditional B-mode US. Administration of ATO to established U87 tumors caused significant vascular shutdown within 2 hrs at all doses in the range 5 to 10 mg/kg in a dose dependant manner, as revealed by depressed bioluminescent light emission. At lower doses substantial recovery was seen within 4 hrs. At 8 mg/kg there was >85% reduction in tumor vascular perfusion, which remained depressed after 6 hrs, but showed some recovery after 24 hrs. Similar response was observed in MCF7 and PC3 tumors. Dynamic BLI and PD US each showed similar duration and percent reductions in tumor blood flow, but FLI showed no significant changes during the first 24 hrs.The results provide further evidence for comparable utility of optical and ultrasound imaging for monitoring tumor growth, More specifically, they confirm the utility of BLI and ultrasound imaging as facile assays of the vascular disruption in solid tumors based on ATO as a model agent.     

兔VX2肝癌模型微波消融后磁共振灌注成像的可行性与应用价值

目的通过兔VX2模型探讨肿瘤消融治疗后动态变化过程中,磁共振灌注成像动态量化研究的可行性及其价值。方法16只新西兰大白兔分为实验组12只,对照组4只。实验组在兔肝脏种植VX2肿瘤后,观察肿瘤直径超过2.0 cm时行微波消融治疗。对比术后当天7、d、14 d及28 d实验组与对照组磁共振灌注成像量化指标—最大增强斜率（MSI）的动态变化差异,并与病理结果对照分析。结果对照组兔及实验组兔术后当天肝实质灌注MSI差异无显著性;实验组兔术前肿瘤与术后当天残留肿瘤的平均MSI差异无显著性;实验组兔残留肿瘤与良性强化组织的MSI差异有显著性。残留肿瘤的时间-信号强度曲线表现为快速上升型;良性强化组织的时间-信号强度曲线表现为缓慢上升型。结论磁共振灌注成像的动态量化研究是可行的,量化指标MSI与消融治疗后各种组织的病理结果相吻合,可更为准确地量化表达病变组织的病理状态的改变。     

动态增强磁共振监测VEGF反义核酸对兔颌面部VX2肿瘤放疗的增敏作用

目的:研究动态增强磁共振成像(dynamic contrast enhanced magnetic resonance imaging,DCE-MRI)监测VEGF反义核酸对兔颌面部VX2肿瘤放疗后的影响。方法:24只颌面部VX2荷瘤兔模型随机分4组:放疗组(A组):给予16Gy放疗;VEGF反义核酸治疗组(B组):肿瘤局部注入VEGF反义核酸150μg;VEGF反义核酸联合放疗组(C组):16Gy放疗后立即局部肿瘤内注射VEGF反义核酸150μg;对照组(D组):肿瘤内注射300μl5%葡萄糖水溶液。治疗后第3天、14天分别行DCE-MRI检查,计算MER(Maximal enhancement ratio,最大强化率)及SLE(Slope of enhancement,强化率斜率)值,14天处死动物行病理检查和VEGF免疫组化染色。结果:C组治疗后14天肿瘤体积明显缩小,与治疗前和治疗后三天及其它组比较差别具有统计学意义(P<0.01)。MER值降低和SLE值降低,与治疗前比较差别有统计学意义(P<0.05)。病理切片显示肿瘤细胞水肿、出血,坏死,血管壁增厚闭塞,VEGF免疫阳性表达下降,经IHS评分与A...     

Dynamic Adjustment of Stimuli in Real Time Functional Magnetic Resonance Imaging

The conventional fMRI image analysis approach to associating stimuli to brain activation is performed by carrying out a massive number of parallel univariate regression analyses. fMRI blood-oxygen-level dependent (BOLD) signal, the basis of these analyses, is known for its low signal-noise-ratio and high spatial and temporal signal correlation. In order to ensure accurate localization of brain activity, stimulus administration in an fMRI session is often lengthy and repetitive. Real-time fMRI BOLD signal analysis is carried out as the signal is observed. This method allows for dynamic, real-time adjustment of stimuli through sequential experimental designs. We have developed a voxel-wise sequential probability ratio test (SPRT) approach for dynamically determining localization, as well as decision rules for stopping stimulus administration. SPRT methods and general linear model (GLM) approaches are combined to identify brain regions that are activated by specific elements of stimuli. Stimulus administration is dynamically stopped when sufficient statistical evidence is collected to determine activation status across regions of interest, following predetermined statistical error thresholds. Simulation experiments and an example based on real fMRI data show that scan volumes can be substantially reduced when compared with pre-determined, fixed designs while achieving similar or better accuracy in detecting activated voxels. Moreover, the proposed approach is also able to accurately detect differentially activated areas, and other comparisons between task-related GLM parameters that can be formulated in a hypothesis-testing framework. Finally, we give a demonstration of SPRT being employed in conjunction with a halving algorithm to dynamically adjust stimuli.     

Monitoring Early Response to Anti-Angiogenic Therapy: Diffusion-Weighted Magnetic Resonance Imaging and Volume Measurements in Colon Carcinoma Xenografts

Objectives

To evaluate the use of diffusion-weighted MRI (DW-MRI) and volume measurements for early monitoring of antiangiogenic therapy in an experimental tumor model.

Materials and Methods

23 athymic nude rats, bearing human colon carcinoma xenografts (HT-29) were examined before and after 6 days of treatment with regorafenib (n = 12) or placebo (n = 11) in a clinical 3-Tesla MRI. For DW-MRI, a single-shot EPI sequence with 9 b-values (10–800 s/mm²) was used. The apparent diffusion coefficient (ADC) was calculated voxelwise and its median value over a region of interest, covering the entire tumor, was defined as the tumor ADC. Tumor volume was determined using T2-weighted images. ADC and volume changes between first and second measurement were evaluated as classifiers by a receiver-operator-characteristic (ROC) analysis individually and combined using Fisher''s linear discriminant analysis (FLDA).

Results

All ADCs and volumes are stated as median±standard deviation. Tumor ADC increased significantly in the therapy group (0.76±0.09×10⁻³ mm²/s to 0.90±0.12×10⁻³ mm²/s; p<0.001), with significantly higher changes of tumor ADC than in the control group (0.10±0.11×10⁻³ mm²/s vs. 0.03±0.09×10⁻³ mm²/s; p = 0.027). Tumor volume increased significantly in both groups (therapy: 347.8±449.1 to 405.3±823.6 mm³; p = 0.034; control: 219.7±79.5 to 443.7±141.5 mm³; p<0.001), however, the therapy group showed significantly reduced tumor growth (33.30±47.30% vs. 96.43±31.66%; p<0.001). Area under the curve and accuracy of the ADC-based ROC analysis were 0.773 and 78.3%; and for the volume change 0.886 and 82.6%. The FLDA approach yielded an AUC of 0.985 and an accuracy of 95.7%.

Conclusions

Regorafenib therapy significantly increased tumor ADC after 6 days of treatment and also significantly reduced tumor growth. However, ROC analyses using each parameter individually revealed a lack of accuracy in discriminating between therapy and control group. The combination of both parameters using FLDA substantially improved diagnostic accuracy, thus highlighting the potential of multi-parameter MRI as an imaging biomarker for non-invasive early tumor therapy monitoring.     

Vibrant技术在磁共振双侧乳腺动态增强检查中的应用及优势

目的：探讨Vibrant 软件技术在磁共振双侧乳腺动态增强检查中的应用及优势。方法：回顾性分析我院经手术或穿刺病理证 实的乳腺疾病患者70 例,均为女性,按照Vibrant 动态增强检查扫描的时间不同,分为A、B 两组,每组35 例。两组病例均采用 1.5T MR 机行动态增强检查。A 组病例行Vibrant 动态增强的扫描时间为9 分24 秒,B组病例行Vibrant 动态增强的扫描时间为 7 分42 秒。结果：A 组病例动态增强MRI 诊断的敏感性为94.74%,特异性为85%,准确性为89.74%;B 组病例动态增强MRI诊 断的敏感性为91.3%,特异性为89.47%,准确性为90.48%。两组病例动态增强MRI对病灶诊断的敏感性、特异性和准确性无显著 性差异（P>0.05）。结论：Vibrant乳腺动态增强扫描技术在乳腺疾病的诊断中具有较高的诊断敏感性、特异性和准确性。Vibrant技 术在缩短增强扫描时间的情况下不降低其诊断效能。     

Diagnosis of Breast Masses from Dynamic Contrast-Enhanced and Diffusion-Weighted MR: A Machine Learning Approach

Purpose

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly used for breast cancer diagnosis as supplementary to conventional imaging techniques. Combining of diffusion-weighted imaging (DWI) of morphology and kinetic features from DCE-MRI to improve the discrimination power of malignant from benign breast masses is rarely reported.

Materials and Methods

The study comprised of 234 female patients with 85 benign and 149 malignant lesions. Four distinct groups of features, coupling with pathological tests, were estimated to comprehensively characterize the pictorial properties of each lesion, which was obtained by a semi-automated segmentation method. Classical machine learning scheme including feature subset selection and various classification schemes were employed to build prognostic model, which served as a foundation for evaluating the combined effects of the multi-sided features for predicting of the types of lesions. Various measurements including cross validation and receiver operating characteristics were used to quantify the diagnostic performances of each feature as well as their combination.

Results

Seven features were all found to be statistically different between the malignant and the benign groups and their combination has achieved the highest classification accuracy. The seven features include one pathological variable of age, one morphological variable of slope, three texture features of entropy, inverse difference and information correlation, one kinetic feature of SER and one DWI feature of apparent diffusion coefficient (ADC). Together with the selected diagnostic features, various classical classification schemes were used to test their discrimination power through cross validation scheme. The averaged measurements of sensitivity, specificity, AUC and accuracy are 0.85, 0.89, 90.9% and 0.93, respectively.

Conclusion

Multi-sided variables which characterize the morphological, kinetic, pathological properties and DWI measurement of ADC can dramatically improve the discriminatory power of breast lesions.     

Validation of Perfusion Quantification with 3D Gradient Echo Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using a Blood Pool Contrast Agent in Skeletal Swine Muscle

The purpose of our study was to validate perfusion quantification in a low-perfused tissue by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with shared k-space sampling using a blood pool contrast agent. Perfusion measurements were performed in a total of seven female pigs. An ultrasonic Doppler probe was attached to the right femoral artery to determine total flow in the hind leg musculature. The femoral artery was catheterized for continuous local administration of adenosine to increase blood flow up to four times the baseline level. Three different stable perfusion levels were induced. The MR protocol included a 3D gradient-echo sequence with a temporal resolution of approximately 1.5 seconds. Before each dynamic sequence, static MR images were acquired with flip angles of 5°, 10°, 20°, and 30°. Both static and dynamic images were used to generate relaxation rate and baseline magnetization maps with a flip angle method. 0.1 mL/kg body weight of blood pool contrast medium was injected via a central venous catheter at a flow rate of 5 mL/s. The right hind leg was segmented in 3D into medial, cranial, lateral, and pelvic thigh muscles, lower leg, bones, skin, and fat. The arterial input function (AIF) was measured in the aorta. Perfusion of the different anatomic regions was calculated using a one- and a two-compartment model with delay- and dispersion-corrected AIFs. The F-test for model comparison was used to decide whether to use the results of the one- or two-compartment model fit. Total flow was calculated by integrating volume-weighted perfusion values over the whole measured region. The resulting values of delay, dispersion, blood volume, mean transit time, and flow were all in physiologically and physically reasonable ranges. In 107 of 160 ROIs, the blood signal was separated, using a two-compartment model, into a capillary and an arteriolar signal contribution, decided by the F-test. Overall flow in hind leg muscles, as measured by the ultrasound probe, highly correlated with total flow determined by MRI, R = 0.89 and P = 10⁻⁷. Linear regression yielded a slope of 1.2 and a y-axis intercept of 259 mL/min. The mean total volume of the investigated muscle tissue corresponds to an offset perfusion of 4.7mL/(min ⋅ 100cm³). The DCE-MRI technique presented here uses a blood pool contrast medium in combination with a two-compartment tracer kinetic model and allows absolute quantification of low-perfused non-cerebral organs such as muscles.     

Vessel Wall Inflammation of Takayasu Arteritis Detected by Contrast-Enhanced Magnetic Resonance Imaging: Association with Disease Distribution and Activity

Aims

The assessment of the distribution and activity of vessel wall inflammation is clinically important in patients with Takayasu arteritis. Magnetic resonance imaging (MRI) is a useful tool, but the clinical utility of late gadolinium enhancement (LGE) in Takayasu arteritis has yet to be determined. The aim of the present study was to evaluate the utility of LGE in assessing vessel wall inflammation and disease activity in Takayasu arteritis.

Methods and Results

We enrolled 49 patients with Takayasu arteritis who had undergone 1.5 T MRI. Patients were divided into Active (n = 19) and Inactive disease (n = 30) groups. The distribution of vessel wall inflammation using angiography and LGE was assessed by qualitative analysis. In 79% and 63% of patients in Active and Inactive groups, respectively, greater distribution of vessel wall inflammation was observed with LGE than with conventional angiography. MRI values of pre- and post-contrast signal-to-noise ratios (SNR), SNR increment (post-SNR minus pre-SNR), pre- and post-contrast contrast-to-noise ratios (CNR), and CNR increment (post-CNR minus pre-CNR) were evaluated at arterial wall sites with the highest signal intensity using quantitative analysis of post-contrast LGE images. No statistically significant differences in MRI parameters were observed between Active and Inactive groups. Contrast-enhanced MRI was unable to accurately detect active disease.

Conclusion

Contrast-enhanced MRI has utility in detecting the distribution of vessel wall inflammation but has less utility in assessing disease activity in Takayasu arteritis.     

Detection of Lung Tumors in Mice Using a 1-Tesla Compact Magnetic Resonance Imaging System

Due to their small size, lung tumors in rodents are typically investigated using high-field magnetic resonance (MR) systems (4.7 T or higher) to achieve higher signal-to-noise ratios, although low-field MR systems are less sensitive to susceptibility artifacts caused by air in the lung. We investigated the feasibility of detecting lung tumors in living, freely breathing mice with a 1-T compact permanent magnet MR system. In total, 4 mice were used, and MR images of mouse lungs were acquired using a T1-weighted three-dimensional fast low-angle shot sequence without cardiac or respiratory gating. The delineation and size of lung tumors were assessed and compared with histopathological findings. Submillimeter lesions were demonstrated as hyperintense, relative to the surrounding lung parenchyma, and were delineated clearly. Among the 13 lesions validated in histopathological sections, 11 were detected in MR images; the MR detection rate was thus 84.6%. A strong correlation was obtained in size measurements between MR images and histological sections. Thus, a dedicated low-field MR system can be used to detect lung tumors in living mice noninvasively without gating.     

A Polymer-Based Magnetic Resonance Tracer for Visualization of Solid Tumors by 13C Spectroscopic Imaging

Morphological imaging precedes lesion-specific visualization in magnetic resonance imaging (MRI) because of the superior ability of this technique to depict tissue morphology with excellent spatial and temporal resolutions. To achieve lesion-specific visualization of tumors by MRI, we investigated the availability of a novel polymer-based tracer. Although the ¹³C nucleus is a candidate for a detection nucleus because of its low background signal in the body, the low magnetic resonance sensitivity of the nucleus needs to be resolved before developing a ¹³C-based tracer. In order to overcome this problem, we enriched polyethylene glycol (PEG), a biocompatible polymer, with ¹³C atoms. ¹³C-PEG40,000 (¹³C-PEG with an average molecular weight of 40 kDa) emitted a single ¹³C signal with a high signal-to-noise ratio due to its ability to maintain signal sharpness, as was confirmed by in vivo investigation, and displayed a chemical shift sufficiently distinct from that of endogenous fat. ¹³C-PEG40,000 intravenously injected into mice showed long retention in circulation, leading to its effective accumulation in tumors reflecting the well-known phenomenon that macromolecules accumulate in tumors because of leaky tumor capillaries. These properties of ¹³C-PEG40,000 allowed visualization of tumors in mice by ¹³C spectroscopic imaging. These findings suggest that a technique based on ¹³C-PEG is a promising strategy for tumor detection.