Project description:Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive method to assess angiogenesis, which is widely used in clinical applications including diagnosis, monitoring therapy response and prognosis estimation in cancer patients. Contrast agents play a crucial role in DCE-MRI and should be carefully selected in order to improve accuracy in DCE-MRI examination. Over the past decades, there was much progress in the development of optimal contrast agents in DCE-MRI. In this review, we describe the recent research advances in this field and discuss properties of contrast agents, as well as their advantages and disadvantages. Finally, we discuss the research perspectives for improving this promising imaging method.
Project description:PURPOSE:The goal of this study was to develop a fast MR fingerprinting (MRF) method for simultaneous T1 and T2 mapping in DCE-MRI studies in mice. METHODS:The MRF sequences based on balanced SSFP and fast imaging with steady-state precession were implemented and evaluated on a 7T preclinical scanner. The readout used a zeroth-moment-compensated variable-density spiral trajectory that fully sampled the entire k-space and the inner 10?×?10 k-space with 48 and 4 interleaves, respectively. In vitro and in vivo studies of mouse brain were performed to evaluate the accuracy of MRF measurements with both fully sampled and undersampled data. The application of MRF to dynamic T1 and T2 mapping in DCE-MRI studies were demonstrated in a mouse model of heterotopic glioblastoma using gadolinium-based and dysprosium-based contrast agents. RESULTS:The T1 and T2 measurements in phantom showed strong agreement between the MRF and the conventional methods. The MRF with spiral encoding allowed up to 8-fold undersampling without loss of measurement accuracy. This enabled simultaneous T1 and T2 mapping with 2-minute temporal resolution in DCE-MRI studies. CONCLUSION:Magnetic resonance fingerprinting provides the opportunity for dynamic quantification of contrast agent distribution in preclinical tumor models on high-field MRI scanners.
Project description:Dynamic myraidpro contrast-enhanced magnetic resonance imaging (DCE-MRI) has been correlated with prognosis in head and neck squamous cell carcinoma as well as with changes in normal tissues. These studies implement different software, either commercial or in-house, and different scan protocols. Thus, the generalizability of the results is not confirmed. To assist in the standardization of quantitative metrics to confirm the generalizability of these previous studies, this data descriptor delineates in detail the DCE-MRI digital imaging and communications in medicine (DICOM) files with DICOM radiation therapy (RT) structure sets and digital reference objects (DROs), as well as, relevant clinical data that encompass a data set that can be used by all software for comparing quantitative metrics. Variable flip angle (VFA) with six flip angles and DCE-MRI scans with a temporal resolution of 5.5?s were acquired in the axial direction on a 3T MR scanner with a field of view of 25.6?cm, slice thickness of 4?mm, and 256×256 matrix size.
Project description:The growth of metastatic tumors in mice can result in markedly increased lymph flow through tumor-draining lymph nodes (LNs), which is associated with LN lymphangiogenesis. A dynamic magnetic resonance imaging (MRI) assay was developed, which uses low-molecular weight gadolinium contrast agent to label the lymphatic drainage, to visualize and quantify tumor-draining lymph flow in vivo in mice bearing metastatic melanomas. Tumor-bearing mice showed greatly increased lymph flow into and through draining LNs and into the bloodstream. Quantitative analysis established that both the amount and the rate of lymph flow through draining LNs are significantly increased in melanoma-bearing mice. In addition, the rate of appearance of contrast media in the bloodstream was significantly increased in mice bearing melanomas. These results indicate that gadolinium-based contrast-enhanced MRI provides a noninvasive assay for high-resolution spatial identification and mapping of lymphatic drainage and for dynamic measurement of changes in lymph flow associated with cancer or lymphatic dysfunction in mice. Low-molecular weight gadolinium contrast is already used for 1.5-T MRI scanning in humans, which should facilitate translation of this imaging assay.
Project description:Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides quantitative metrics (e.g. Ktrans, ve) via pharmacokinetic models. We tested inter-algorithm variability in these quantitative metrics with 11 published DCE-MRI algorithms, all implementing Tofts-Kermode or extended Tofts pharmacokinetic models. Digital reference objects (DROs) with known Ktrans and ve values were used to assess performance at varying noise levels. Additionally, DCE-MRI data from 15 head and neck squamous cell carcinoma patients over 3 time-points during chemoradiotherapy were used to ascertain Ktrans and ve kinetic trends across algorithms. Algorithms performed well (less than 3% average error) when no noise was present in the DRO. With noise, 87% of Ktrans and 84% of ve algorithm-DRO combinations were generally in the correct order. Low Krippendorff's alpha values showed that algorithms could not consistently classify patients as above or below the median for a given algorithm at each time point or for differences in values between time points. A majority of the algorithms produced a significant Spearman correlation in ve of the primary gross tumor volume with time. Algorithmic differences in Ktrans and ve values over time indicate limitations in combining/comparing data from distinct DCE-MRI model implementations. Careful cross-algorithm quality-assurance must be utilized as DCE-MRI results may not be interpretable using differing software.
Project description:PurposeTo investigate the value of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for evaluating denervated skeletal muscle in rabbits.Materials and methods24 male rabbits were randomly divided into an irreversible neurotmesis group and a control group. In the experimental group, the sciatic nerves of rabbits were transected for irreversible neurotmesis model. A sham operation was performed in the control group. MRI of rabbit lower legs was performed before nerve surgery and 1 day, 3 days, 5 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks after surgery.ResultsSignal intensity changes were seen in the left gastrocnemius muscle on the T2-weighted images. DCE-MRI derived parameters (Ktrans, Kep, and Vp) were measured in vivo. In the irreversible neurotmesis group, T2-weighted images showed increased signal intensity in the left gastrocnemius muscle. Ktrans, Vp values changes occur as early as 1 day after denervation, and increased gradually until 4 weeks after surgery. There are significant increases in both Ktrans and Vp values compared with those in the control group after surgery (P < 0.05). Kep values show no significant difference between the irreversible neurotmesis group and the control group.ConclusionDCE-MRI hold the promise of an early and sensitive diagnosis of denervated skeletal muscle.
Project description:BackgroundDynamic contrast-enhanced (DCE) MRI may provide prognostic insights into tumour radiation response. This study examined quantitative DCE MRI parameters in rat tumours, as potential biomarkers of tumour growth delay following single high-dose irradiation.MethodsDunning R3327-AT1 prostate tumours were evaluated by DCE MRI following intravenous injection of Gd-DTPA. The next day tumours were irradiated (single dose of 30 Gy), while animals breathed air (n=4) or oxygen (n=4); two animals were non-irradiated controls. Growth was followed and tumour volume-quadrupling time (T4) was compared with pre-irradiation DCE assessments.ResultsIrradiation caused significant tumour growth delay (T4 ranged from 28 to 48 days for air-breathing rats, and 40 to 75 days for oxygen-breathing rats) compared with the controls (T4=7 to 9 days). A strong correlation was observed between T4 and extravascular-extracellular volume fraction (ve) irrespective of the gas inhaled during irradiation. There was also a correlation between T4 and volume transfer constant (K(trans)) for the air-breathing group alone.ConclusionsThe data provide rationale for expanded studies of other tumour sites, types and progressively patients, and are potentially significant, as many patients undergo contrast-enhanced MRI as part of treatment planning.
Project description:The prediction of monoclonal antibody (mAb) disposition within solid tumors for individual patients is difficult due to inter-patient variability in tumor physiology. Improved a priori prediction of mAb pharmacokinetics in tumors may facilitate the development of patient-specific dosing protocols and facilitate improved selection of patients for treatment with anti-cancer mAb. Here, we report the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with tumor penetration of the contrast agent gadobutrol used as a surrogate, to improve physiologically based pharmacokinetic model (PBPK) predictions of cetuximab pharmacokinetics in epidermal growth factor receptor (EGFR) positive xenografts. In the initial investigations, mice bearing Panc-1, NCI-N87, and LS174T xenografts underwent DCE-MRI imaging with the contrast agent gadobutrol, followed by intravenous dosing of an 125Iodine-labeled, non-binding mAb (8C2). Tumor concentrations of 8C2 were determined following the euthanasia of mice (3 h-6 days after 8C2 dosing). Potential predictor relationships between DCE-MRI kinetic parameters and 8C2 PBPK parameters were evaluated through covariate modeling. The addition of the DCE-MRI parameter Ktrans alone or Ktrans in combination with the DCE-MRI parameter Vp on the PBPK parameters for tumor blood flow (QTU) and tumor vasculature permeability (σTUV) led to the most significant improvement in the characterization of 8C2 pharmacokinetics in individual tumors. To test the utility of the DCE-MRI covariates on a priori prediction of the disposition of mAb with high-affinity tumor binding, a second group of tumor-bearing mice underwent DCE-MRI imaging with gadobutrol, followed by the administration of 125Iodine-labeled cetuximab (a high-affinity anti-EGFR mAb). The MRI-PBPK covariate relationships, which were established with the untargeted antibody 8C2, were implemented into the PBPK model with considerations for EGFR expression and cetuximab-EGFR interaction to predict the disposition of cetuximab in individual tumors (a priori). The incorporation of the Ktrans MRI parameter as a covariate on the PBPK parameters QTU and σTUV decreased the PBPK model prediction error for cetuximab tumor pharmacokinetics from 223.71 to 65.02%. DCE-MRI may be a useful clinical tool in improving the prediction of antibody pharmacokinetics in solid tumors. Further studies are warranted to evaluate the utility of the DCE-MRI approach to additional mAbs and additional drug modalities.
Project description:Background We aimed to improve the assessment quality of plaque vulnerability with combined use of magnetic resonance imaging and contrast-enhanced ultrasound ( CEUS ). Methods and Results We prospectively enrolled 71 patients with internal carotid artery stenosis who underwent carotid endarterectomy and performed preoperative CEUS and magnetic resonance plaque imaging. We distinguished high-signal-intensity plaques ( HIP s) and non- HIP s based on magnetization-prepared rapid acquisition with gradient echo images. We graded them according to the CEUS contrast effect and compared the CEUS images with the carotid endarterectomy specimens. Among the 70 plaques, except 1 carotid endarterectomy tissue sample failure, 59 were classified as HIP s (43 symptomatic) and 11 were classified as non- HIP s (5 symptomatic). Although the magnetization-prepared rapid acquisition with gradient echo findings alone had no significant correlation with symptoms ( P=0.07), concomitant use of magnetization-prepared rapid acquisition with gradient echo and CEUS findings did show a significant correlation ( P<0.0001). CEUS showed that all 5 symptomatic non- HIP s had a high-contrast effect. These 5 plaques were histopathologically confirmed as vulnerable, with extensive neovascularization but only a small amount of intraplaque hemorrhage. Conclusions Complementary use of magnetic resonance imaging and CEUS to detect intraplaque hemorrhage and neovascularization in plaques can be useful for evaluating plaque vulnerability, consistent with the destabilization process associated with neovessel formation and subsequent intraplaque hemorrhage.
Project description:Key pointsThe blood-brain barrier (BBB) is an important and dynamic structure which contributes to homeostasis in the central nervous system. BBB permeability changes occur in health and disease but measurement of BBB permeability in humans is not straightforward. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to model the movement of gadolinium contrast into the brain, expressed as the influx constant Ki . Here evidence is provided that Ki as measured by DCE-MRI behaves as expected for a marker of overall BBB leakage. These results support the use of DCE-MRI for in vivo studies of human BBB permeability in health and disease.AbstractBlood-brain barrier (BBB) leakage can be measured using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as the influx constant Ki . To validate this method we compared measured Ki with biological expectations, namely (1) higher Ki in healthy individual grey matter (GM) versus white matter (WM), (2) GM/WM cerebral blood volume (CBV) ratio close to the histologically established GM/WM vascular density ratio, (3) higher Ki in visibly enhancing multiple sclerosis (MS) lesions versus MS normal appearing white matter (NAWM), and (4) higher Ki in MS NAWM versus healthy individual NAWM. We recruited 13 healthy individuals and 12 patients with MS and performed whole-brain 3D DCE-MRI at 3 T. Ki and CBV were calculated using Patlak modelling for manual regions of interest (ROI) and segmented tissue masks. Ki was higher in control GM versus WM (P = 0.001). CBV was higher in GM versus WM (P = 0.005, mean ratio 1.9). Ki was higher in visibly enhancing MS lesions versus MS NAWM (P = 0.002), and in MS NAWM versus controls (P = 0.014). Bland-Altman analysis showed no significant difference between ROI and segmentation methods (P = 0.638) and an intra-class correlation coefficient showed moderate single measure consistency (0.610). Ki behaves as expected for a compound marker of permeability and surface area. The GM/WM CBV ratio measured by this technique is in agreement with the literature. This adds evidence to the validity of Ki measured by DCE-MRI as a marker of overall BBB leakage.