Dynamic Contrast-enhanced Perfusion Imaging Research Articles

A proof-of-concept pipeline to guide evaluation of tumor tissue perfusion by dynamic contrast-agent imaging: Direct simulation and inverse tracer-kinetic procedures.

Dynamic contrast-enhanced (DCE) perfusion imaging has shown great potential to non-invasively assess cancer development and its treatment by their characteristic tissue signatures. Different tracer kinetics models are being applied to estimate tissue and tumor perfusion parameters from DCE perfusion imaging. The goal of this work is to provide an in silico model-based pipeline to evaluate how these DCE imaging parameters may relate to the true tissue parameters. As histology data provides detailed microstructural but not functional parameters, this work can also help to better interpret such data. To this aim in silico vasculatures are constructed and the spread of contrast agent in the tissue is simulated. As a proof of principle we show the evaluation procedure of two tracer kinetic models from in silico contrast-agent perfusion data after a bolus injection. Representative microvascular arterial and venous trees are constructed in silico. Blood flow is computed in the different vessels. Contrast-agent input in the feeding artery, intra-vascular transport, intra-extravascular exchange and diffusion within the interstitial space are modeled. From this spatiotemporal model, intensity maps are computed leading to in silico dynamic perfusion images. Various tumor vascularizations (architecture and function) are studied and show spatiotemporal contrast imaging dynamics characteristic of in vivo tumor morphotypes. The Brix II also called 2CXM, and extended Tofts tracer-kinetics models common in DCE imaging are then applied to recover perfusion parameters that are compared with the ground truth parameters of the in silico spatiotemporal models. The results show that tumor features can be well identified for a certain permeability range. The simulation results in this work indicate that taking into account space explicitly to estimate perfusion parameters may lead to significant improvements in the perfusion interpretation of the current tracer-kinetics models.

Clinical Application of Dynamic Contrast Enhanced Perfusion Imaging by Cardiovascular Magnetic Resonance.

Functionally significant coronary artery disease impairs myocardial blood flow and can be detected non-invasively by myocardial perfusion imaging. While multiple myocardial perfusion imaging modalities exist, the high spatial and temporal resolution of cardiovascular magnetic resonance (CMR), combined with its freedom from ionising radiation make it an attractive option. Dynamic contrast enhanced CMR perfusion imaging has become a well-validated non-invasive tool for the assessment and risk stratification of patients with coronary artery disease and is recommended by international guidelines. This article presents an overview of CMR perfusion imaging and its clinical application, with a focus on chronic coronary syndromes, highlighting its strengths and challenges, and discusses recent advances, including the emerging role of quantitative perfusion analysis.

Differentiation between benign and malignant ovarian masses using multiparametric MRI

PurposeTo investigate the capabilities of multiparametric MRI including dynamic contrast enhanced (DCE) perfusion and diffusion-weighted imaging (DWI) to discriminate between benign and malignant ovarian masses. MethodsA total of 43 women with a total of 43 ovarian masses were retrospectively included. They had a mean age of 51.26±18.05 (SD) years (range: 20–88years). Twenty women had benign and 23 had malignant ovarian tumors. All women had multiparametric MRI examinations including DWI (b50-b800) and DCE perfusion imaging at 1–5T. Results of DWI (apparent diffusion coefficient [ADC], b-800) and DCE imaging (volume transfer coefficient [Ktrans], rate constant [Kep], interstitial volume [Ve], initial area under the curve [iAUC]) were compared between benign and malignant ovarian masses. ResultsMean ADC was significantly lowed in malignant tumors (0.92±0.25 [SD]×10−3 mm2/s (range: 0.6–1.6×10−3 mm2/s) than in benign tumors (1.37±0.69 [SD]×10−3 mm2/s; range: 0.4–2.9×10−3 mm2/s) (P=0.011). B-800 was significantly greater in malignant tumors (80.61±24.73 [SD] s/mm2; range: 24–110 s/mm2) than in benign ones (61.15±22.17 [SD] s/mm2; range: 38–155 s/mm2) (P=0.010). Ktrans was lower in benign tumors (0.13±0.06 [SD] min−1; range: 0–0.2min−1) than in malignant ones (0.25±0.16 [SD] min−1; range: 0.1–0.8min−1) (P=0.002). Kep was significantly greater in malignant tumors (0.55±0.19 [SD] min−1; range: 0.1–1.9min−1) than in benign ones (0.44±0.38 [SD] min−1; range: 0.2–1.1min−1) (P=0.003). iAUC was greater in malignant tumors (15.59±7.98 [SD] mM/min; range: 6.6–42.1mM/min) than in benign ones (7.98±5.06 [SD] mM/min; range: 0.2–17.7mM/min) (P=0.001). No differences in Ve were found between benign and malignant masses (P=0.084). The area under the ROC curve was significant for all parameters but Ve. Logistic regression analysis revealed 5.590 and 11.637 times higher malignancy risk for an ADC≤0.93×10−3 mm2/s and an iAUC≥13.88mM/min, respectively. ConclusionMultiparametric MRI has high accuracy in discrimination between benign and malignant ovarian masses. Therefore, adding these methods to the more common MRI protocol can help select the best treatment option in women with ovarian mass.

Fractional Perfusion: A Simple Semi-Parametric Measure for Hyperpolarized 13C MR

Hyperpolarized <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">13</sup> C magnetic resonance imaging is a promising tool for in-vivo metabolic interrogation of disease states and treatment efficacy assessment. The method is currently limited by the lack of good quantitative measures, particularly in humans where large variations in transport kinetics have been reported. Here, we introduce a novel model-free method for quantification of metabolic information in dynamic hyperpolarized imaging data. Fractional perfusion is defined as the metabolic conversion corrected for substrate delivery, and is achieved by scaling the area under the curve of the hyperpolarized signals with the tissue perfusion. Rats subjected to unilateral ischemia reperfusion injury (IRI) were used. The proposed fractional perfusion was investigated using hyperpolarized [1- <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">13</sup> C]pyruvate and α-trideuteromethyl[15N]glutamine, and then compared with 1H dynamic contrast enhanced perfusion imaging. We demonstrate that hyperpolarized <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">13</sup> C-metabolites can be used to quantify the energy demand by mapping both the injected biomarker perfusion and the metabolic conversion such that the pyruvate concentration curve can be a surrogate marker for perfusion in cases where other perfusion assessment is not directly obtainable. In the case of IRI, the obtained perfusion parameters allowed the fractional perfusion approach to differentiate an alteration in metabolic conversion by accounting for differences in pyruvate delivery.

Extended quantitative dynamic contrast-enhanced cardiac perfusion imaging in mice using accelerated data acquisition and spatially distributed, two-compartment exchange modeling.

The objective of the present work was to improve data acquisition and quantification of dynamic contrast-enhanced perfusion imaging in the in vivo murine heart. Four-fold undersampled data were acquired in 14 mice and reconstructed using k-t SPARSE. A two-compartment exchange model was employed to provide additional characterization of myocardial tissue based on compartment volumes and the permeability surface area product. The feasibility of the proposed method was tested using compartment-based analysis of contrast-enhanced perfusion data acquired with intravascular and extracellular contrast agents. A significantly different permeability surface area product was measured for the intravascular versus extracellular contrast agent (0.13-0.15ml/g/min vs 0.86-0.88ml/g/min). The reduced extravasation also resulted in significantly smaller interstitial volumes of the intravascular versus extracellular agent (9.8-11% vs 45-47%). No difference was found for myocardial blood flow (6.5-7.2ml/g/min vs 6.0-7.0ml/g/min). The results presented here show that two-compartment exchange modeling in the in vivo murine heart is feasible and gives access to tissue parameters beyond myocardial blood flow.

Advanced magnetic resonance imaging (MRI) of soft tissue tumors: techniques and applications.

Imaging evaluation of soft tissue tumors is important for the diagnosis, staging, and follow-up. Magnetic resonance imaging (MRI) is the preferred imaging modality due to its multiplanarity and optimal tissue contrast resolution. However, standard morphological sequences are often not sufficient to characterize the exact nature of the lesion, addressing the patient to an invasive bioptic examination for the definitive diagnosis. The recent technological advances with the development of functional MRI modalities such as diffusion-weighted imaging, dynamic contrast-enhanced perfusion imaging, magnetic resonance spectroscopy, and diffusion tensor imaging with tractography have implemented the multiparametricity of MR to evaluate in a noninvasive manner the biochemical, structural, and metabolic features of tumor tissues. The purpose of this article is to review the state of the art of these advanced MRI techniques, with focus on their technique and clinical application.

Feasibility of quantitative MR-perfusion imaging to monitor treatment response after uterine artery embolization (UAE) in symptomatic uterus fibroids

IntroductionIn 25% of women, symptomatic uterus myomas are diagnosed with clinical and functional impairment ranging from abdominal and pelvic pain to dys- and hypermenorrhea, dyspareunia, pollakiuria and infertility. Women undergoing a treatment increasingly prefer nowadays minimal invasive, uterus preserving therapies like uterine artery embolization (UAE) over surgical hysterectomy, nowadays. To emphasize the efficacy of UAE as a uterus preserving treatment with targeted therapy of myomas only, analysis of tissue perfusion pre and post embolization is required. The purpose of this study was to assess treatment response in UAE in females with symptomatic uterus myomas by quantitative magnetic resonance perfusion imaging. MethodsSeven females scheduled for uterus myoma embolization underwent three MRI examinations (pre, post, follow-up) including morphological and dynamic contrast enhanced perfusion imaging at 3 T. To measure tumor volume, regions-of-interest covering the tumor and the uterus were drawn by two readers in consensus. Blood flow, blood volume, and mean transit time were calculated by a pixel-by-pixel deconvolution approach. Kruskal-Wallis/Friedman test was employed to test whether the group medians differ significantly with correction for multiple comparisons using Bonferroni method. ResultsChange of volume could be observed in all patients after embolization but was significantly different only between pre/post and follow-up time point. Measured differences in all perfusion parameters were significant between pre-intervention and post-intervention/follow-up in the myomas, no significant differences could be detected for the uterus tissue. ConclusionsOur results demonstrate devascularization of symptomatic myomas which correlates with cessation of hypermenorrhea in all treated patients without affecting healthy uterus tissue. Supplementing UAE with perfusion imaging to monitor early treatment response is feasible and might provide valuable information for the follow-up of patients and contribute to providing confidence for the patients in treatment success.

Isotropically weighted intravoxel incoherent motion brain imaging at 7T

Perfusion magnetic resonance imaging (MRI) is a promising non-invasive technique providing insights regarding the brain's microvascular architecture in vivo. The scalar perfusion metrics can be used for quantitative diagnostics of various brain abnormalities, in particular, in the stroke cases and tumours. However, conventional MRI-based perfusion approaches such as dynamic contrast-enhanced perfusion imaging or arterial spin labelling have a few weaknesses, for instance, contrast agent deposition, low signal-to-noise ratio, limited temporal and spatial resolution, and specific absorption rate constraints. As an alternative, the intravoxel incoherent motion (IVIM) approach exploits an extension of diffusion MRI in order to estimate perfusion parameters in the human brain. Application of IVIM imaging at ultra-high field MRI might employ the advantage of a higher signal-to-noise ratio, and thereby the use of higher spatial and temporal resolutions.In the present work, we demonstrate an application of recently developed isotropic diffusion weighted sequences to the evaluation of IVIM parameters at an ultra-high 7T field. The used sequence exhibits high immunity to image degrading factors and allows one to acquire the data in a fast and efficient way. Utilising the bi-exponential fitting model of the signal attenuation, we performed an extensive analysis of the IVIM scalar metrics obtained by a isotropic diffusion weighted sequence in vivo and compared results with a conventional pulsed gradient sequence at 7T. In order to evaluate a possible metric bias originating from blood flows, we additionally used a truncated b-value protocol (b-values from 100 to 200 s/mm2 with the step 20 s/mm2) accompanied to the full range (b-values from 0 to 200 s/mm2). The IVIM scalar metrics have been assessed and analysed together with a large and middle vessel density atlas of the human brain. We found that the diffusion coefficients and perfusion fractions of the voxels consisting of large and middle vessels have higher values in contrast to other tissues. Additionally, we did not find a strong dependence of the IVIM metrics on the density values of the vessel atlas. Perspectives and limitations of the developed isotropic diffusion weighted perfusion are presented and discussed.

Transient Neurologic Deficit without Vascular Pathology Correlates with Reversible Focal Hypoperfusion on Arterial Spin Labeled Perfusion Imaging

AbstractWe present the case of a 16-year-old boy with altered mental status and magnetic resonance imaging demonstrating left hemispheric hypoperfusion without evidence of stroke, based on arterial spin labeling (ASL) and dynamic contrast-enhanced perfusion imaging. Vessel imaging on magnetic resonance angiography and computed tomography angiography, in addition to an echocardiogram, showed no evidence of an embolic source. Electroencephalography showed left posterior temporal slowing. Within 8 hours, he was awake and alert but with receptive aphasia, and within 24 hours his symptoms completely resolved. Repeat ASL perfusion imaging demonstrated complete resolution of the perfusion abnormality, and diffusion imaging revealed no areas of infarct. This report demonstrates the correlation between a transient neurologic deficit and reversible focal hypoperfusion measured by ASL cerebral perfusion.

De Novo Assessment of Pediatric Musculoskeletal Soft Tissue Tumors: Beyond Anatomic Imaging.

MRI plays a central role in the assessment of pediatric musculoskeletal soft tissue tumors. Although these neoplasms may initially be evaluated on other modalities, such as sonography, MRI is essential for accurately determining the extent of disease. Traditionally, MRI has been performed with sequences that provide excellent anatomic detail, with T1-weighted, fluid-sensitive, and static postcontrast T1-weighted sequences. However, with the introduction of noncontrast sequences such as diffusion-weighted imaging and magnetic resonance spectroscopy to the arsenal of available MRI techniques, functional and metabolic features of a neoplasm can now be examined noninvasively. These more recent MRI methods offer information for lesion characterization, the assessment of treatment response, and the distinction of postoperative scar from recurrence. Dynamic contrast-enhanced perfusion imaging is another useful functional technique that can be acquired before conventional static postcontrast imaging, without requiring additional contrast material. This review presents recent advances in MRI methodology that enable a comprehensive clinical assessment of musculoskeletal tumors in the pediatric population. The roles and challenges of combining anatomic, functional, and metabolic MRI sequences will be discussed as they relate to newly discovered soft tissue tumors in children.

Diagnosis of brain tumors using dynamic contrast-enhanced perfusion imaging with a short acquisition time.

This study sought to determine the diagnostic utility of perfusion parameters derived from dynamic contrast-enhanced (DCE) perfusion MRI with a short acquisition time (approximately 3.5 min) in patients with glioma, brain metastasis, and primary CNS lymphoma (PCNSL).Twenty-six patients with 29 lesions (4 low-grade glioma, 13 high-grade glioma, 7 metastasis, and 5 PCNSL) underwent DCE-MRI in a 3 T scanner. A ROI was placed on the hotspot of each tumor in maps for volume transfer contrast Ktrans, extravascular extracellular volume Ve, and fractional plasma volume Vp. We analyzed differences in parameters between tumors using the Mann–Whitney U test. We calculated sensitivity and specificity using receiver operating characteristics analysis.Mean Ktrans values of LGG, HGG, metastasis and PCNSL were 0.034, 0.31, 0.38, 0.44, respectively. Mean Ve values of each tumors was 0.036, 0.57, 0.47, 0.96, and mean Vp value of each tumors was 0.070, 0.086, 0.26, 0.17, respectively. Compared with other tumor types, low-grade glioma showed lower Ktrans (P < 0.01, sensitivity = 88%, specificity = 100%) and lower Ve (P < 0.01, sensitivity = 96%, specificity = 100%). PCNSL showed higher Ve (P < 0.01, sensitivity = 100%, specificity = 88%), but the other perfusion parameters overlapped with those of different histology.Kinetic parameters derived from DCE-MRI with short acquisition time provide useful information for the differential diagnosis of brain tumors.

Simultaneous Measurement of Kidney Function by Dynamic Contrast Enhanced MRI and FITC-Sinistrin Clearance in Rats at 3 Tesla: Initial Results

Glomerular filtration rate (GFR) is an essential parameter of kidney function which can be measured by dynamic contrast enhanced magnetic resonance imaging (MRI-GFR) and transcutaneous approaches based on fluorescent tracer molecules (optical-GFR). In an initial study comparing both techniques in separate measurements on the same animal, the correlation of the obtained GFR was poor. The goal of this study was to investigate if a simultaneous measurement was feasible and if thereby, the discrepancies in MRI-GFR and optical-GFR could be reduced. For the experiments healthy and unilateral nephrectomised (UNX) Sprague Dawley (SD) rats were used. The miniaturized fluorescent sensor was fixed on the depilated back of an anesthetized rat. A bolus of 5 mg/100 g b.w. of FITC-sinistrin was intravenously injected. For dynamic contrast enhanced perfusion imaging (DCE-MRI) a 3D time-resolved angiography with stochastic trajectories (TWIST) sequence was used. By means of a one compartment model the excretion half-life (t1/2) of FITC-sinistrin was calculated and converted into GFR. GFR from DCE-MRI was calculated by fitting pixel-wise a two compartment renal filtration model. Mean cortical GFR and GFR by FITC-sinistrin were compared by Bland-Altman plots and pair-wise t-test. Results show that a simultaneous GFR measurement using both techniques is feasible. Mean optical-GFR was 4.34±2.22 ml/min (healthy SD rats) and 2.34±0.90 ml/min (UNX rats) whereas MRI-GFR was 2.10±0.64 ml/min (SD rats) and 1.17±0.38 ml/min (UNX rats). Differences between healthy and UNX rats were significant (p<0.05) and almost equal percentage difference (46.1% and 44.3%) in mean GFR were assessed with both techniques. Overall mean optical-GFR values were approximately twice as high compared to MRI-GFR values. However, compared to a previous study, our results showed a higher agreement. In conclusion, the possibility to use the transcutaneous method in MRI may have a huge impact in improving and validating MRI methods for GFR assessment in animal models.

A Comparative Evaluation of Ultrasound Molecular Imaging, Perfusion Imaging, and Volume Measurements in Evaluating Response to Therapy in Patient-Derived Xenografts

Most pre-clinical therapy studies use the change in tumor volume as a measure for disease response. However, tumor size measurements alone may not reflect early changes in tumor physiology that occur as a response to treatment. Ultrasonic molecular imaging (USMI) and Dynamic Contrast Enhanced-Perfusion Imaging (DCE-PI) with ultrasound are two attractive alternatives to tumor volume measurements. Since these techniques can provide information prior to the appearance of gross phenotypic changes, it has been proposed that USMI and DCE-PI could be used to characterize response to treatment earlier than traditional methods. This study evaluated the ability of tumor volume measurements, DCE-PI, and USMI to characterize response to therapy in two different types of patient-derived xenografts (known responders and known non-responders). For both responders and non-responders, 7 animals received a dose of 30 mg/kg of MLN8237, an investigational aurora-A kinase inhibitor, for 14 days or a vehicle control. Volumetric USMI (target integrin:α av β3) and DCE-PI were performed on day 0, day 2, day 7, and day 14 in the same animals. For USMI, day 2 was the earliest point at which there was a statistical difference between the untreated and treated populations in the responder cohort (Untreated: 1.20 ± 0.53 vs. Treated: 0.49 ± 0.40; p < 0.05). In contrast, statistically significant differences between the untreated and treated populations as detected using DCE-PI were not observed until day 14 (Untreated: 0.94 ± 0.23 vs. Treated: 1.31 ± 0.22; p < 0.05). Volume measurements alone suggested no statistical differences between treated and untreated populations at any readpoint. Monitoring volumetric changes is the "gold standard" for evaluating treatment in pre-clinical studies, however, our data suggests that volumetric USMI and DCE-PI may be used to earlier classify and robustly characterize tumor response.

Comparative study of three dimensional dynamic contrast-enhanced MR perfusion imaging in healthy volunteers and patients with chronic obstructive pulmonary disease

Objective To prospectively compare MR pulmonary perfusion imaging with quantitative HRCT for the detection of mild chronic obstructive pulmonary disease (COPD) and classification of COPD. Methods Sixty-two consecutive patients with COPD and 17 healthy volunteers underwent pulmonary function test (PFT),HRCT and MR perfusion imaging on the same day.According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD),all COPD patients were classified into 4 stages:stageⅠ (n=19),stageⅡ (n=17),stageⅢ (n=14),stageⅣ Key words: Pulmonary disease,chronic obstructive; Respiratory function tests; Magnetic resonance imaging; Tomography,X-ray computed

SU-FF-J-137: Rapid Prototyping of Vascular Trees for Quality Assurance of Dynamic Contrast Enhanced Perfusion Imaging and Analysis

Purpose: The increasing need for a quantitative imaging validation tool is fueled by the propagation of perfusion imaging for cancer treatment, prognosis and evaluation. Current methods of providing validation for dynamic contrast‐enhanced (DCE) imaging and analyses have been limited to simulated data, which do not account for variances in image acquisition and artifacts, and static phantoms, which do not yet monitor dynamic effects and their analyses. This work investigates Rapid Prototyping (RP) techniques as a means of creating a high‐order branched vascular phantom amenable to modular integration of regions with differential perfusion. Method and Materials: Three dimensional computerized vascular trees were generated. Each successive bifurcation produced vessels with a smaller inner diameter. The tree structure was fabricated using two RP methods: Selective Laser Sintering (SLS) and Fused Deposition Modeling (FDM) using polycaprolactone (PCL) and ABSplus, respectively. Tests of the phantoms included evaluation of occlusion for the smaller diameter vessels, as well as DCE CT for end‐to‐end testing with perfusion analysis software. Results: Three orders of branching were produced. The build accuracy of the phantoms were assessed with physical measurements and determined to be approximately +/− 200 microns. Vessels with inner diameters of 900 microns were successfully created. DCE CT demonstrated usable flow data across the increasing levels of bifurcation.Conclusion: RP has been successfully tested as a means to generate vascular networks in association with construction of a perfusion phantom for quality assurance of DCE imaging and analysis. Current efforts include development of modular elements for generation of the capillary‐tissue interface. Supported by NIH P01‐CA59827 and the Gates Foundation.

Reproducibility of MR perfusion and 1H spectroscopy of bone marrow

To determine the reproducibility of proton ((1)H) magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in a clinical setting for the assessment of marrow fat fraction and marrow perfusion in longitudinal studies. In all, 36 subjects (17 females, 19 males, mean age 72.9 +/- 2.9 years) who underwent MR spectroscopy and/or dynamic contrast-enhanced perfusion imaging of the proximal femur were asked to return after 1 week for a repeat MR examination. Reproducibility of (1)H MR spectroscopy in all bone areas tested was high, ranging from 0.78-0.85, with the highest reproducibility being in the femoral head and lowest in the femoral neck. Reproducibility of paired perfusion measurements ranged from 0.59 (enhancement slope femoral head) to 0.98 (enhancement maximum acetabulum). Overall reproducibility of (1)H MR spectroscopy and dynamic contrast-enhanced imaging tended to be best in areas with the highest inherent fat fraction or perfusion. Reproducibility of (1)H MR spectroscopy or perfusion imaging is sufficiently high to warrant these techniques being applied to the longitudinal study of bone diseases.