Operator dependency of arterial input function in dynamic contrast-enhanced MRI

Objective

To investigate the effect of inter-operator variability in arterial input function (AIF) definition on kinetic parameter estimates (KPEs) from dynamic contrast-enhanced (DCE) MRI in patients with high-grade gliomas.

Methods

The study included 118 DCE series from 23 patients. AIFs were measured by three domain experts (DEs), and a population AIF (pop-AIF) was constructed from the measured AIFs. The DE-AIFs, pop-AIF and AUC-normalized DE-AIFs were used for pharmacokinetic analysis with the extended Tofts model. AIF-dependence of KPEs was assessed by intraclass correlation coefficient (ICC) analysis, and the impact on relative longitudinal change in K^trans was assessed by Fleiss’ kappa (κ).

Results

There was a moderate to substantial agreement (ICC 0.51–0.76) between KPEs when using DE-AIFs, while AUC-normalized AIFs yielded ICC 0.77–0.95 for K^trans, k_ep and v_e and ICC 0.70 for v_p. Inclusion of the pop-AIF did not reduce agreement. Agreement in relative longitudinal change in K^trans was moderate (κ = 0.591) using DE-AIFs, while AUC-normalized AIFs gave substantial (κ = 0.809) agreement.

Discussion

AUC-normalized AIFs can reduce the variation in kinetic parameter results originating from operator input. The pop-AIF presented in this work may be applied in absence of a satisfactory measurement.

     

Multi-Slice DCE-MRI Data Using P760 Distinguishes Between Metastatic and Non-Metastatic Rodent Prostate Tumors

An intermediate molecular weight contrast agent P760 was used to investigate the ability of multi-slice dynamic contrast-enhanced MRI (DCE-MRI) to distinguish metastatic from non-metastatic rodent prostate tumors. Non-metastatic AT2.1 and metastatic AT3.1 prostate tumors originally derived from the Dunning prostate cancer model were implanted on the hind leg of Copenhagen rats. Multi-sliced DCE-MRI data were acquired on a SIGNA 1.5 T scanner and analyzed using a recently developed empirical mathematical model. The P760 multi-slice DCE-MRI data in combination with the empirical mathematical model successfully distinguished between metastatic and non-metastatic rodent prostate tumors. Specifically, fitting the data with the empirical model showed that metastatic tumors had significantly faster contrast media uptake (p<0.001) and slower washout rates (p<0.01) than non-metastatic tumors     

Distribution of gadomelitol in a human breast tumor model in mice

The study evaluates the tumor distribution of the rapid clearance blood pool agent (RCBPA) gadomelitol, in a breast tumor model. Different techniques were used : (1) tissue gadolinium concentrations measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES), (2) whole body quantitative autoradiography using radiolabeled [¹⁵³Gd] gadomelitol and (3) dynamic contrast-enhanced MRI with compartmental analysis. An accumulation of gadomelitol in tumors compared to muscle was observed 30 min and 3 h post injection (p.i.). Thirty minutes p.i., the gadomelitol tumor distribution evaluated by autoradiography showed a marked difference between the rim and the center, whereas both areas showed comparable concentrations after 3 h. Using dynamic contrast-enhanced MRI, three phases could be observed during the 1 hour observation period: (1) rapid tumor uptake within the first few minutes post-injection (2) a progressive increase in tumor signal enhancement over 10 min and (3) a steady-state phase. Average +/− SD (n=5) transendothelial permeability K^PS and the fractional blood volume fBV were 12.2±1.6 μl/min⁻¹/g and 5.4±0.2% respectively. Due to its slow extravasation and high tumor residence time, gadomelitol may potentially be useful to improve characterization between benign versus malignant tumors using dynamic MRI.     

Dynamic contrast-enhanced MRI using macromolecular contrast media for monitoring the response to isolated limb perfusion in experimental soft-tissue sarcomas

The objective of this study was to evaluate the potential of dynamic contrast-enhanced MRI for quantitative characterization of tumor microvessels and to assess the microvascular changes in response to isolated limb perfusion with TNF- and melphalan. Dynamic contrast-enhanced MRI was performed in an experimental cancer model, using a macromolecular contrast medium, albumin-(Gd-DTPA)₄₅. Small fragments of BN 175, a soft-tissue sarcoma, were implanted in 11 brown Norway (BN) rats. Animals were assigned randomly to a control (Haemaccel) or drug-treated group (TNF-/melphalan). MRI was performed at baseline and 24 h after ILP. The transendothelial permeability (K^PS) and the fractional plasma volume (fPV) were estimated from the kinetic analysis of MR data using a two-compartment bi-directional model. K^PS and fPV decreased significantly in the drug-treated group compared to baseline (p<0.05). In addition, K^PS post therapy was significantly lower (p<0.05) in the drug-treated group than in the control group. There was no significant difference in fPV between the drug-treated and the control group after therapy. Tumor microvascular changes in response to isolated limb perfusion can be determined after 24 h by dynamic contrast-enhanced MRI. The data obtained in this experimental model suggest possible applications in the clinical setting, using the appropriate MR contrast agents.     

Contrast enhancement in atherosclerosis development in a mouse model: in vivo results at 2 Tesla

To develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE^–/– mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T1 spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 m spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice.     

A novel framework for evaluating the image accuracy of dynamic MRI and the application on accelerated breast DCE MRI

Objective

To develop a novel framework for evaluating the accuracy of quantitative analysis on dynamic contrast-enhanced (DCE) MRI with a specific combination of imaging technique, scanning parameters, and scanner and software performance and to test this framework with breast DCE MRI with Time-resolved angiography WIth Stochastic Trajectories (TWIST).

Materials and methods

Realistic breast tumor phantoms were 3D printed as cavities and filled with solutions of MR contrast agent. Full k-space raw data of individual tumor phantoms and a uniform background phantom were acquired. DCE raw data were simulated by sorting the raw data according to TWIST view order and scaling the raw data according to the enhancement based on pharmaco-kinetic (PK) models. The measured spatial and temporal characteristics from the images reconstructed using the scanner software were compared with the original PK model (ground truth).

Results

Images could be reconstructed using the manufacturer’s platform with the modified ‘raw data.’ Compared with the ‘ground truth,’ the RMS error in all images was <10% in most cases. With increasing view-sharing acceleration, the error of the initial uptake slope decreased while the error of peak enhancement increased. Deviations of PK parameters varied with the type of enhancement.

Conclusion

A new framework has been developed and tested to more realistically evaluate the quantitative measurement errors caused by a combination of the imaging technique, parameters and scanner and software performance in DCE-MRI.

     

Cervical carcinoma: standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival

Since detailed knowledge regarding the pathophysiological properties—which in turn are responsible for differences in contrast enhancement—remain fairly undetermined, it was the aim of this study (i) to examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis (microvessel density [MVD]; vascular endothelial growth factor [VEGF]) and (ii) to determine the ultimate value of a histomorphological and a dynamic MRI approach by correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude A, exchange rate constantk ₂₁) and standard parameters (maximum signal intensity (SI)-increase, [SI-I] over baseline and steepest SI-upslope, per second [SI-U/s]) were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with similar sized and positioned regions-of-interest (ROIs) on the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found betweenMVD and amplitudeA (P<0.01) andSI-I (P<0.05). No significant relationships were observed between theVEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based onk ₂₁ and SI-U/s showed that tumors with highk ₂₁ andSI-U/s values had a significantly (P<0.05, 0.001, respectively) worse disease outcome than tumors with lowk ₂₁ andSI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD, VEGF) had any significant power to predict patient survival. It is concluded that (1) the pathophysiological basis for differences in dynamic MRI isMVD but not VEGF-expression; (2) a functional, dynamic MRI approach (both standard and a pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis; and [3] compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assessMVD or patient survival.     

Detection of myocardial viability in acute infarction using contrast-enhanced <Superscript>1</Superscript>H magnetic resonance imaging

Background Reperfusion strategies salvage myocardium at risk in acute myocardial infarction (MI). This clinical study was performed to determine whether areas without evidence of delayed MRI contrast enhancement in MI correspond to viability by means of percent systolic wall thickening (%SWT) and enddiastolic wall thickness (EDWT) in chronic infarction. Methods Twenty MRI studies were performed in ten patients within 6 days of MI and 3 months post-MI. On a segmental basis the percentage of viable myocardium as defined by contrast-enhanced MRI (no delayed MRI contrast enhancement) in acute MI was measured and was compared with %SWT and EDWT in chronic MI. Results Of the 1718 segments in acute infarction in which the percentage of viable myocardium was measured 1333 were found to be completely viable by means of contrast-enhanced MRI (no delayed MRI contrast enhancement). All of these segments revealed %SWT on day 90 post-MI, and 97% of segments were viable by means of an EDWT of more than 5.5 mm. In 85 segments the proportion of viable myocardium was 50–99% (mean 56±8%), with 92% segments found to be viable by means of %SWT and 92% by EDWT, and of 156 segments with viable myocardium between 1–49% (36±8%) 79% were found to be viable by means of %SWT and 82% by EDWT. Corresponding proportions of 144 segments with transmural delayed MRI contrast enhancement in acute MI were 45% and 17%. Conclusions In acute reperfused MI viable myocardium as delineated by contrast-enhanced MRI is correlated with clinical parameters of viability. Delayed MRI contrast enhancement resolves nontransmural MI and may become a valuable clinical tool when planning revascularization procedures.     

Magnetic resonance imaging at 1.5 T with immunospecific contrast agent in vitro and in vivo in a xenotransplant model

Object: Demonstrating the feasibility of magnetic resonance imaging (MRI) at 1.5 T of ultrasmall particle iron oxide (USPIO)-antibody bound to tumor cells in vitro and in a murine xenotransplant model. Methods: Human D430B cells or Raji Burkitt lymphoma cells were incubated in vitro with different amounts of commercially available USPIO-anti-CD20 antibodies and cell pellets were stratified in a test tube. For in vivo studies, D430B cells and Raji lymphoma cells were inoculated subcutaneously in immunodeficient mice. MRI at 1.5 T was performed with T1-weighted three-dimensional fast field echo sequences (17/4.6/13°) and T2-weighted three-dimensional fast-field echo sequences (50/12/7°). For in vivo studies MRI was performed before and 24 h after USPIO-anti-CD20 administration. Results: USPIO-anti-CD20-treated D430B cells, showed a dose-dependent decrease in signal intensity (SI) on T2*-weighted images and SI enhancement on T1-weighted images in vitro. Raji cells showed lower SI changes, in accordance to the fivefold lower expression of CD20 on Raji with respect to D430B cells. In vivo 24 h after USPIO-anti-CD20 administration, both tumors showed an inhomogeneous decrease of SI on T2*-weighted images and SI enhancement on T1-weighted images. Conclusions: MRI at 1.5 T is able to detect USPIO-antibody conjugates targeting a tumor-associated antigen in vitro and in vivo.     

MR imaging of the prostate in clinical practice

Magnetic resonance imaging (MRI) is the imaging tool of choice in the evaluation of prostate cancer. The main applications of MR imaging in the management of prostate cancer are: (1) to guide targeted biopsy when prostate cancer is clinically suspected and previous ultrasound-guided biopsy results are negative; (2) to localize and stage prostate cancer and provide a roadmap for treatment planning; and (3) to detect residual or locally recurrent cancer after treatment. Other MR techniques such as proton MR spectroscopic imaging (MRSI), diffusion-weighted imaging (DWI), and contrast-enhanced MRI (CE-MRI) complement conventional MR imaging by providing metabolic and functional information that can improve the accuracy of prostate cancer detection and characterization. In everyday clinical practice, and to account for patient comfort, MR imaging studies are limited to 1 h. To obtain consistently high-quality images, a well-designed protocol is necessary. Routine MR imaging can be supplemented by other MR techniques such as MRSI, DWI or CE-MRI depending on the expertise available and the clinical questions that need to be answered. This review summarizes the role of MR imaging in the management of prostate cancer and describes practical approaches to implementing anatomic, metabolic and functional MR imaging techniques in the clinic.     

Magnetic resonance imaging in patients with granulomatosis with polyangiitis (Wegener’s) and subglottic stenosis

Objective

To evaluate the ability of MRI to detect subglottic stenosis and to differentiate between active and inactive subglottic inflammation in patients with granulomatosis with polyangiitis (GPA).

Materials and methods

MRI studies of the larynx of 18 GPA patients with suspected SGS were included. The MRI protocol included T1- and T2-weighted and STIR-sequences, dynamic contrast enhancement (DCE) and diffusion weighted imaging (DWI). Two independent observers reviewed the MR images. SGS were identified and quantified, inflammatory activity was assessed using edema imaging, DCE and DWI. Final MRI diagnoses were compared to the clinical, laryngoscopic and histopathologic results.

Results

MRI confirmed SGS in all GPA patients with significant narrowing of the airway lumen and thickening of subglottic wall. Assessing the subglottic inflammatory activity, MRI showed a sensitivity of 87.5 % and a specificity of 60.0 %. Interrater agreement was κ = 0.769. Of the different MR technical approaches tested, edema imaging was most sensitive and specific. DWI led to significant differences in the apparent diffusion coefficient between active and inactive subglottic inflammation. No significant differences were found with DCE imaging.

Conclusion

MR imaging has shown the ability to detect and grade SGS in patients with GPA. It non-invasively assesses the status of inflammatory activity utilizing edema sensitive sequences and DWI.     

High proton relaxivity for gadolinium oxide nanoparticles

Objective: Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The objective of the present study was to investigate proton relaxation enhancement by ultrasmall (5 to 10 nm) Gd₂O₃ nanocrystals. Materials and methods: Gd₂O₃ nanocrystals were synthesized by a colloidal method and capped with diethylene glycol (DEG). The oxidation state of Gd₂O₃ was confirmed by X-ray photoelectron spectroscopy. Proton relaxation times were measured with a 1.5-T MRI scanner. The measurements were performed in aqueous solutions and cell culture medium (RPMI). Results: Results showed a considerable relaxivity increase for the Gd₂O₃–DEG particles compared to Gd-DTPA. Both T ₁ and T ₂ relaxivities in the presence of Gd₂O₃–DEG particles were approximately twice the corresponding values for Gd–DTPA in aqueous solution and even larger in RPMI. Higher signal intensity at low concentrations was predicted for the nanoparticle solutions, using experimental data to simulate a T₁-weighted spin echo sequence. Conclusion: The study indicates the possibility of obtaining at least doubled relaxivity compared to Gd–DTPA using Gd₂O₃–DEG nanocrystals as contrast agent. The high T ₁ relaxation rate at low concentrations of Gd₂O₃ nanoparticles is very promising for future studies of contrast agents based on gadolinium-containing nanocrystals.     

Effects of restricted diffusion in a biological phantom: a q-space diffusion MRI study of asparagus stems at a 3T clinical scanner

Introduction The aim of this work was to study the effects of restricted diffusion in a biological phantom consisting of green asparagus stems using q-space MRI at a clinical scanner. Method Measurements of the full width at half maximum (FWHM) of the displacement distribution were performed with varied diffusion time (T _d). The accuracy of the measurements was investigated with respect to the degree of violation of the short gradient pulse (SGP) condition, partial volume effects and a FWHM-based tensor model. Results The measurements showed a reasonably constant FWHM perpendicular to the capillaries in the vascular bundles and an increased FWHM parallel with the bundles when the T _d was increased. A 15% decrease in FWHM perpendicular to the bundles was observed when the diffusion encoding duration was prolonged from 24 to 74 ms, owing to the violation of the SGP condition. For a population of different confinement sizes, simulations indicated that the FWHM reflects the smaller sizes rather then the mean size of the confinements. Conclusion A new method allowing tensor analysis of FWHM was derived and yielded accurate results. In conclusion, we found it possible to measure the effects of restricted diffusion with q-space MRI using a clinical MRI scanner.     

Integrated head-thoracic vascular MRI at 3 T: Assessment of cranial, cervical and thoracic involvement of giant cell arteritis

Recently, high-resolution contrast-enhanced MRI has proven to be feasible for noninvasive diagnosis of giant cell arteritis in the cranium. In such examinations, thickening of the vessel wall and/or increased contrast enhancement demonstrate mural inflammation. Typically, the superficial cranial arteries with predominance of the superficial temporal artery are affected by the disease. However, giant cell arteritis can also involve other parts of the vascular system and an examination with extended coverage, including head, neck, and thorax would be advantageous. In this study, a novel approach for integrated head-thoracic vascular MRI at 3 T is presented. Combining first-pass imaging of a single-dose contrast agent with post-contrast imaging permits the assessment of both thoracic aortic geometry and wall, in addition to high-resolution head imaging needed for the analysis of the small superficial cranial arteries. Results from a patient feasibility study are presented and confirm that the protocol can successfully be completed in less than 40 min. Supported through by a grant from the Deutsche Forschungsgemeinschaft (DFG) Grant # MA 2383/3-1     

Enhancement characteristics of hepatic focal nodular hyperplasia and its scar by dynamic magnetic resonance imaging

Rationale and objectives: To determine the relationship between the lesion and the scar enhancement characteristics in a series of hepatic Focal Nodular Hyperplasia (FNH) lesions studied with dynamic MR imaging.Methods: Nine patients with FNH were studied. The slice showing the largest scar was selected for the dynamic single slice T1-weighted Gradient-echo sequence before and after contrast administration (15 images, one every 20 s). Analysis was performed with ROI measurements in the lesion and the scar. Signal-intensity and enhancement curves were obtained from both structures.Results: Dynamic MRI showed the typical homogeneous early enhancement of the lesion with delayed enhancement of the scar. The scar enhanced early and vigorously in all cases. Two patterns of enhancement curves were defined. In the parallel pattern, both curves started early, quickly reaching a plateau maintained over time (77.8%). In the divergent pattern the curve of the scar was above the curve of the FNH (22.2%). after the maximum slope was reached, with progressive separation of the curves.Conclusion: There is a hypervascular scar enhancement within FNH lesions with either a parallel or divergent course after the maximum early enhancement.     

High-resolutation magnetic resonance imaging of the endolymphatic duct and sac

An anatomical study was carried out to determine the extent to which magnetic resonance imaging (MRI) could delineate inner ear structures. Anatomical preparations of human petrous temporal bone were examined and compared with the results of MRI in 20 healthy subjects to see whether the structures of the inner ear could be visualized. Imaging of the subjects was carried out in a 1.0-T MRI scanner (Siemens Magnetom Impact). Two stronglyT ₂*-weighted sequences were used: a 3D-PSIF sequence and a 3D-CISS sequence. The 3D data sets were postprocessed using a Maximum Intensity Projection (MIP) program. Our investigations show that it is possible to obtain accurate visualization of structures with a diameter of under 1 mm. In all 20 subjects it was possible to identify both the endolymphatic duct and the endolymphatic sac.     

Proton magnetic resonance spectroscopy of the central,transition and peripheral zones of the prostate: assignments and correlation with histopathology

Proton magnetic resonance spectroscopy (MRS) is used to compare the chemistry of the transition, central and peripheral zones of the prostate. The assignments are made using two-dimensional correlated spectroscopy and the results compared with histopathology. The chemistry associated with benign prostatic hyperplasia (BPH), prostate intraepithelial neoplasia (PIN) and malignant biopsy tissues are described. There are distinct MR spectral patterns for glandular and stromal BPH, PIN and adenocarcinoma. Importantly, there are also different spectral patterns from BPH in the transitional and central zones when compared to BPH in the peripheral zone. A pattern recognition method is used to analyze the MR spectra from the biopsy specimens. The resultant mathematical classifiers generated a high level of accuracy (sensitivity and specificity of 100 and 97%). It was found that for this accuracy to be achieved, the classifiers need to be developed by comparing the spectra with specialist serial sectioned histopathology. With serial sectioned pathology the pattern recognition method was capable of identifying less than 5% of adenocarcinoma in a given piece of tissue. Many of the chemicals identified in the biopsy specimens are available for inspection from the prostate, in vivo, at 3 T.     

Long-term follow-up of patients with acute myocarditis by magnetic resonance imaging

Magnetic resonance imaging (MRI) reveals cardiac signal intensity changes in patients with acute myocarditis; however, the natural history of these changes and their relationship to individual outcomes are unknown. The relationship of MRI findings to long-term outcome was studied by serial MRI studies in 16 patients with acute myocarditis who were followed for 30±4 (SE) months. Myocardial contrast enhancement was monitored using contrast-enhanced T1-weighted fast spin-echo images. Left ventricular ejection fraction was measured with gradient-echo sequences. Clinical symptoms were scored. The results were compared to a control group of 26 age-matched, healthy volunteers. Myocardial contrast enhancement, which was markedly increased in the early course of the disease, decreased at 4 weeks and remained within the normal range in most patients after 30 months. Contrast enhancement 4 weeks after onset of symptoms was predictive for the functional and clinical long-term outcome. Contrast-enhanced MRI may be a useful, noninvasive tool for long-term follow-up of patients with acute myocarditis. Furthermore, relatively early MRI findings may predict longer-term outcomes. Electronic Publication     

Data analysis for dynamic contrast-enhanced MRI-based cerebral perfusion measurements: correcting for changing cortical CSF volumes

The time evolution of the histogram (number of pixels versus signal intensity) is used to calculate ΔR ₂ parameters from dynamic contrast-enhanced magnetic resonance (MR) imaging of the brain. This method partially corrects for partial volume effects and is an improvement over the approach using the signal intensity as a function of time when confounding factors such as changing cortical cerebrospinal fluid volumes are involved. The maximum value for ΔR ₂ is found to correlate with relative cerebral blood flow as assessed by xenon inhalation and can be used to discriminate between vascular dementia and healthy volunteers. With this method, the normal range for ΔR ₂ values is found to be the same for both young (19–40 years old) and elderly (65–85 years old) healthy volunteers.