Contrast Enhancement In MR Images Research Articles

Yolk–shell magnetic composite Fe3O4@Co/Zn-ZIF for MR imaging-guided chemotherapy of tumors in vivo

The yolk–shell composites Fe3O4@Co/Zn-ZIF exhibited high doxorubicin loading capacity, pH-responsive release characteristics, and strong T2-weighted MR imaging contrast enhancement, and were used for MR imaging-guided chemotherapy of tumors in vivo.

Synthesis method of novel Gd2O3@Fe3O4 nanocomposite modified by dextrose capping agent

In current study, gadolinium oxide was heterogeneously formed on the surface of iron oxide nanoparticles and further modified with dextrose capping agent to be used in biomedical applications, especially for contrast enhancement in MR images. First, two types of iron oxide nanoparticles were prepared at 25 and 80 °C via simple coprecipitaion method. Then, gadolinium oxide nanoparticles were synthesized through a consecutive precipitation process on previously formed iron oxide seeds in an aqueous media and subsequent annealing at 300 °C. Finally, dextrose was used as capping agent to stabilize nanocomposites in a colloidal suspension. X-ray diffraction (XRD), Scanning and Transmission electron microscopy, Dynamic Laser Scattering (DLS), Fourier-Transform Infrared Spectroscopy (FTIR), and Magnetometery (VSM) techniques were employed for nanocomposites investigation and MTT-assay method used for viability assessment of colloidal samples. Measurements based on Scherrer equation from XRD patterns showed that increasing coprecipitation temperature resulted bigger iron oxide crystallites. The iron oxide crystallite size was increased from 15.1 to 28.1 nm. Precipitation process led to gadolinium oxide formation with 30.7 and 38.8 nm crystallite sizes, respectively. TEM images revealed that iron oxide agglomerates were encapsulated in gadolinium oxide surroundings. Hydrodynamic size of the coated nanoparticles with dextrose was 208 and 247 nm. In VSM examinations, nanocomposites did not display coercive field and the saturation magnetization was 1.93 emu/g. MTT-assay results showed 80% viability in 285 μg nanocomposites containing 96.9 μg [Fe] and 11.4 μg [Gd].

Synthesis and Assessment of Peptide Gd-DOTA Conjugates Targeting Extradomain B Fibronectin for Magnetic Resonance Molecular Imaging of Prostate Cancer.

Contrast enhanced MRI is commonly used in imaging and treatment planning of prostate cancer. However, no tumor targeting contrast agent is commercially available for accurate detection and characterization of prostate cancer with MRI. Extradomain B fibronectin (EDB-FN), an oncoprotein present in aggressive tumors, is a promising molecular target for detection and stratification of high-risk prostate cancer. In this work, we have identified four small peptides (GVK, IGK, SGV, and ZD2) specific to EDB-FN for tumor targeting. In silico simulations of the binding patterns and affinities of peptides to the EDB protein fragment revealed different binding site to different peptide in the ligand-receptor interactions. Tumor specificity and organ distribution of the peptides were assessed using fluorescence imaging in male mice bearing PC-3 human prostate cancer xenografts. Targeted contrast agents were synthesized by conjugating tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to the peptides in the solid phase, followed by complexation with GdCl3. The contrast agents were characterized by MALDI-TOF mass spectrometry and relaxivity measurements. All four peptide Gd-DOTA conjugates resulted in robust tumor contrast enhancement in MR imaging of the PC3 mouse prostate cancer model. The peptide Gd-DOTA conjugates specific to EDB-FN are promising targeted small molecular macrocyclic contrast agents for MR molecular imaging of prostate cancer.

18F-FDG PET and MR imaging associations across a spectrum of pediatric brain tumors: a report from the pediatric brain tumor consortium.

The purpose of this study was to describe (18)F-FDG uptake across a spectrum of pediatric brain tumors and correlate (18)F-FDG PET with MR imaging variables, progression-free survival (PFS), and overall survival (OS). A retrospective analysis was conducted of children enrolled in phase I/II clinical trials through the Pediatric Brain Tumor Consortium from August 2000 to June 2010. PET variables were summarized within diagnostic categories using descriptive statistics. Associations of PET with MR imaging variables and PFS and OS by tumor types were evaluated. Baseline (18)F-FDG PET was available in 203 children; 66 had newly diagnosed brain tumors, and 137 had recurrent/refractory brain tumors before enrolling in a Pediatric Brain Tumor Consortium trial. MR imaging was performed within 2 wk of PET and before therapy in all cases. The (18)F-FDG uptake pattern and MR imaging contrast enhancement (CE) varied by tumor type. On average, glioblastoma multiforme and medulloblastoma had uniform, intense uptake throughout the tumor, whereas brain stem gliomas (BSGs) had low uptake in less than 50% of the tumor and ependymoma had low uptake throughout the tumor. For newly diagnosed BSG, correlation of (18)F-FDG uptake with CE portended reduced OS (P = 0.032); in refractory/recurrent BSG, lack of correlation between (18)F-FDG uptake and CE suggested decreased PFS (P = 0.023). In newly diagnosed BSG for which more than 50% of the tumor had (18)F-FDG uptake, there was a suggestion of lower apparent diffusion coefficient (P = 0.061) and decreased PFS (P = 0.065). (18)F-FDG PET and MR imaging showed a spectrum of patterns depending on tumor type. In newly diagnosed BSG, the correlation of (18)F-FDG uptake and CE suggested decreased OS, likely related to more aggressive disease. When more than 50% of the tumor had (18)F-FDG uptake, the apparent diffusion coefficient was lower, consistent with increased cellularity. In refractory/recurrent BSG, poor correlation between (18)F-FDG uptake and CE was associated with decreased PFS, which may reflect concurrent tissue breakdown at sites of treated disease and development of new sites of (18)F-FDG-avid malignancy.

White and gray matter contrast enhancement in MR images of the mouse brain in vivo using IR UTE with a cryo-coil at 9.4 T.

The aim of this work was to assess the capability of high field MRI to image brain micro-structures containing various amount of myelin. A cryogenic RF receiver coil (Bruker 'CryoProbe') and an ultra-short echo (UTE) 2D pulse sequence with and without inversion pulse were used for coronal brain MR imaging of a healthy C57BL/6J mouse. A 9.4 T magnet system was used. Signal-to-noise ratio (SNR) within the selected regions was measured. A room temperature volume RF coil was also used for SNR comparison. The inversion recovery IR-UTE 2D pulse sequence was optimized for maximum white matter (WM) and gray matter (GM) contrast-to-noise ratio (CNR). The results showed 3- to 12-fold improvement in SNR for the cryo-coil compared to the volume coil depending on the area. The inversion times providing optimum CNR for WM and GM were found to be 500 ms (negative CNR) and 1000 ms (positive CNR) for the echo time of 350 μs. Presented method provide better SNR and CNR for the brain structures with short T2 than the current techniques. The results indicate that the optimized IR-UTE pulse sequence when used with the cryo-coil allows for over 10-fold enhancement of the CNR for WM and GM as compared to the standard UTE without inversion pulse.

Role of O-(2-18F-Fluoroethyl)-l-Tyrosine PET as a Diagnostic Tool for Detection of Malignant Progression in Patients with Low-Grade Glioma

In patients with low-grade glioma (LGG) of World Health Organization (WHO) grade II, early detection of progression to WHO grade III or IV is of high clinical importance because the initiation of a specific treatment depends mainly on the WHO grade. In a significant number of patients with LGG, however, information on tumor activity and malignant progression cannot be obtained on the basis of clinical or conventional MR imaging findings only. We here investigated the potential of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET to noninvasively detect malignant progression in patients with LGG. Twenty-seven patients (mean age ± SD, 44 ± 15 y) with histologically proven LGG (WHO grade II) were investigated longitudinally twice using dynamic (18)F-FET PET and routine MR imaging. Initially, MR imaging and PET scans were performed, and diagnosis was confirmed on the basis of biopsy. Subsequently, PET scans were obtained when clinical findings or contrast-enhanced MR imaging suggested malignant progression. Maximum and mean tumor-to-brain ratios (20-40 min after injection) (TBRmax and TBRmean, respectively) of (18)F-FET uptake as well as tracer uptake kinetics (i.e., time to peak [TTP] and patterns of the time-activity curves) were determined. The diagnostic accuracy of imaging parameters for the detection of malignant progression was evaluated by receiver-operating-characteristic analyses and by Fisher exact test for 2 × 2 contingency tables. In patients with histologically proven malignant progression toward WHO grade III or IV (n = 18), TBRmax and TBRmean increased significantly, compared with baseline (TBRmax, 3.8 ± 1.0 vs. 2.4 ± 1.0; TBRmean, 2.2 ± 0.3 vs. 1.6 ± 0.6; both P < 0.001), whereas TTP decreased significantly (median TTP, 35 vs. 23 min; P < 0.001). Furthermore, time-activity curve patterns changed significantly in 10 of 18 patients (P < 0.001). The combined analysis of (18)F-FET PET parameters (i.e., changes of TBRmax, TTP, or time-activity curve pattern) yielded a significantly higher diagnostic accuracy for the detection of malignant progression than changes of contrast enhancement in MR imaging (accuracy, 81% vs. 63%; P = 0.003). Both tumor-to-brain ratio and kinetic parameters of (18)F-FET PET uptake provide valuable diagnostic information for the noninvasive detection of malignant progression of LGG. Thus, repeated (18)F-FET PET may be helpful for further treatment decisions.

The prognostic value of tumor necrosis in patients undergoing stereotactic radiosurgery of brain metastases

BackgroundThis retrospective study investigated the outcome of patients with brain metastases after radiosurgery with special emphasis on prognostic impact of visible intratumoral necrosis on survival and local control.MethodsFrom 1998 through 2008, 149 patients with brain metastases from solid tumors were treated with stereotactic radiotherapy at Luebeck University. Median age was 58.4 years with 11%, 78%, 10% in recursive partitioning analysis (RPA) classes I, II, III, respectively. 70% had 1 metastasis, 29% 2-3 metastases, 2 patients more than 3 metastases, 71% active extracranial disease. Median volume of metastatic lesions was 4.7 cm3, median radiosurgery dose 22 Gy (single fraction). 71% of patients received additional whole-brain irradiation (WBI). All patients were analyzed regarding survival, local, distant failure and prognostic factors, side effects and changes in neurologic symptoms after radiotherapy. The type of contrast-enhancement in MR imaging was also analyzed; metastatic lesions were classified as containing necrosis if they appeared as ring-enhancing with central areas of no or minimal contrast enhancement.ResultsMedian survival was 7.0 months with 1-year and 5-year survival rates of 33% and 0.4%, respectively. Tumor necrosis (ring-enhancement) was visible on pretreatment MRI scans in 56% of all lesions and lesions with necrosis were larger than non-necrotic lesions (6.7 cm3 vs. 3.2 cm3, p = 0.01). Patients with tumor necrosis had a median survival of 5.4 months, patients without tumor necrosis 7.2 months. Local control rate in the irradiated volume was 70%, median survival without local failure 17.8 months. Control in the brain outside the irradiated volume was 60%, median survival without distant failure 14.0 months. Significant prognostic factors for overall survival were KPS (p = 0.001), presence of tumor necrosis on pretreatment MRI (p = 0.001) with RPA-class and WBI reaching marginal significance (each p = 0.05). Prognostic impact of tumor necrosis remained significant if only smaller tumors with a volume below 3.5 cm3 (p = 0.03). Side effects were rare, only one patient suffered from serious acute side effects.ConclusionsResults of this retrospective study support that stereotactic radiotherapy is an effective treatment option for patients with metastatic brain lesions. The prognostic impact of visible tumor necrosis (ring-enhancement) on pretreatment MRI scans should be further investigated.

Evaluation of 3′-deoxy-3′-[18F]-fluorothymidine (18F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas

The thymidine analog 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) has been developed as a positron emission tomography (PET) tracer to assess the proliferation activity of tumors in vivo. The present study investigated the relationship between the kinetic parameters of (18)F-FLT in vivo and thymidine kinase-1 (TK-1) expression and cell proliferation rate in vitro, and blood-brain barrier (BBB) breakdown in human brain gliomas. A total of 21 patients with newly diagnosed gliomas were examined by (18)F-FLT PET kinetic analysis. Maximum standardized uptake value (SUVmax) and tumor-to-normal (T/N) ratio of (18)F-FLT in the tumor and (18)F-FLT kinetic parameters in the corresponding contralateral region were determined. The expression levels of TK-1 protein and mRNA were determined by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR), respectively, using surgical specimens. The cell proliferation rate of the tumor was determined in terms of the Ki-67 labeling index. BBB breakdown was evaluated on MR images with contrast enhancement. (18)F-FLT SUVmax and T/N ratio were significantly correlated with the influx rate constant (K (1); P = 0.001 and P < 0.001, respectively), but not with the phosphorylation rate constant (k (3)). IHC and real-time PCR studies demonstrated a significant correlation between K (1) and TK-1 mRNA expression (P = 0.001), but not between k (3) and TK-1 protein and mRNA expression. Linear regression analysis revealed a significant correlation between K (1) and the Ki-67 index (P = 0.003), but not between k (3) and the Ki-67 index. TK-1 mRNA expression was significantly correlated with the Ki-67 index (P = 0.009). (18)F-FLT SUVmax and T/N ratio were significantly correlated with BBB breakdown evaluated by contrast enhancement in MR images (P = 0.003 and P = 0.011, respectively). These results indicate that (18)F-FLT uptake in the tumor is significantly related to transport through the disrupted BBB, but not through phosphorylation activity. Although the tissue TK-1 expression reflects tumor proliferation activity, the phosphorylation rate constant k (3) determined by (18)F-FLT PET kinetic analysis does not accurately reflect TK-1 expression in the tissue and should not be used as a surrogate biomarker of cell proliferation activity in human brain gliomas.

Synthesis and Characterization of New Porphyrazine-Gd(III) Conjugates as Multimodal MR Contrast Agents

Magnetic resonance imaging (MRI) has long been used clinically and experimentally as a diagnostic tool to obtain three-dimensional, high-resolution images of deep tissues. These images are enhanced by the administration of contrast agents such as paramagnetic Gd(III) complexes. Herein, we describe the preparation of a series of multimodal imaging agents in which paramagnetic Gd(III) complexes are conjugated to a fluorescent tetrapyrrole, namely, a porphyrazine (pz). Zinc metalated pzs conjugated to one, four, or eight paramagnetic Gd(III) complexes are reported. Among these conjugates, Zn-Pz-8Gd(III) exhibits an ionic relaxivity four times that of the monomeric Gd(III) agent, presumably because of increased molecular weight and a molecular relaxivity that is approximately thirty times larger, while retaining the intense electronic absorption and emission of the unmodified pz. Unlike current clinical MR agents, Zn-Pz-1Gd(III) is taken up by cells. This probe demonstrates intracellular fluorescence by confocal microscopy and provides significant contrast enhancement in MR images, as well as marked phototoxicity in assays of cellular viability. These results suggest that pz agents possess a new potential for use in cancer imaging by both MRI and near-infrared (NIR) fluorescence, while acting as a platform for photodynamic therapy.

Magnetic resonance imaging dynamics of contrast medium uptake in vestibular schwannomas

Efficacy of radiosurgery in vestibular schwannoma (VS) is usually documented by changes of tumor size and by loss of contrast enhancement in MR imaging within the central portion of the lesion. Until now, however, correlation between contrast enhancement and timing of image acquisition in nontreated VS has not been analyzed systematically. The authors undertook this study to investigate changes in contrast enhancement with respect to latency of image acquisition after contrast agent administration. The dynamics of contrast medium uptake were evaluated with T1-weighted VIBE MR imaging sequences performed immediately and 1.5, 3.5, 4.5, 9.5, and 11.5 minutes after administration of single dose of Gd in 21 patients with nontreated medium- to large-sized VSs. Signal-to-noise (SNR) and contrast-to-noise ratio (CNR) of tumors were evaluated, and volumes of central nonenhancing areas (NEAs) were determined. The interior appearance of the tumors changed considerably over time. The NEA significantly diminished in size (p < 0.0001, Friedman test) and almost completely disappeared in all but 2 patients. Compared to images at 1.5 minutes, NEA volumes decreased to a median of 36% at 3.5 minutes and 34% at 4.5 minutes, showing smaller changes after that-9% at 9.5 minutes and 3% at 11.5 minutes. Tumor SNR and CNR increased over time. The maximum change in the median values for SNR and CNR were a 72% increase and 117% increase, respectively; both occurred at 1.5 minutes after Gd administration. Contrast enhancement in VS MR imaging varies according to the duration of the delay between contrast agent administration and image acquisition. Postradiotherapy changes in contrast enhancement of VS can therefore not be attributed only to effective radiotherapy. So-called "loss of central contrast enhancement" may be falsely detected because of timing. A standardized protocol with defined timing of image acquisition may increase comparability of contrast uptake in VS.

Rational imaging in locally advanced prostate cancer

Prostate cancer is one of the principal medical problems facing the male population in developed countries with an increasing need for sophisticated imaging techniques and risk-adapted treatment options. This article presents an overview of the current imaging procedures in the diagnosis of locally advanced prostate cancer. Apart from conventional gray-scale transrectal ultrasound (TRUS) as the most frequently used primary imaging modality we describe computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). CT and MRI not only allow assessment of prostate anatomy but also a specific evaluation of the pelvic region. Color-coded and contrast-enhanced ultrasound, real-time elastography, dynamic contrast enhancement in MR imaging, diffusion imaging, and MR spectroscopy may lead to a clinically relevant improvement in the diagnosis of prostate cancer. While bone scintigraphy with (99m)Tc-bisphosphonates is still the method of choice in the evaluation of bone metastasis, whole-body MRI and PET using (18)F-NaF, (18)F-FDG, (11)C-choline, (11)C-acetate, and (18)F-choline as tracers achieve higher sensitivities.

Dynamics of contrast enhancement in MR imaging and power Doppler ultrasonography of solid breast lesions

To evaluate the dynamics of contrast enhancement in solid breast lesions at contrast-enhanced MR imaging and power Doppler ultrasonography (US) and to compare the methods to histology and to each other. Forty breast lesions were prospectively examined with dynamic MR and power Doppler US. Time-signal intensity curves of enhancement were obtained for both methods. The shape of the curve was analyzed to be benign, indeterminate or malignant. The curves were also analyzed quantitatively by calculating the slope of the curve and the area under the curve (both methods), relative enhancement (MR), and time to peak (US). The lesions were divided into malignant lesions, fibroadenomas, and other benign lesions. The results were compared to histology. In the subjective analysis of the MR curve in differentiating between benign and malignant lesions the accuracy was 90%. The MR curve also enabled differentiation between fibroadenomas and malignancies. The accuracy of the US curve was 38%. Quantitatively, statistically significant differences were found using all the MR variables, except between malignancies and fibroadenomas. Using the US variables, no significant difference was found between the groups. The dynamics of contrast-enhanced MR were reliable in the differential diagnosis of solid breast lesions, but contrast-enhanced power Doppler US was of limited value.

Dynamics of contrast enhancement in MR imaging and power Doppler ultrasonography of solid breast lesions

Purpose: To evaluate the dynamics of contrast enhancement in solid breast lesions at contrast-enhanced MR imaging and power Doppler ultrasonography (US) and to compare the methods to histology and to each other. Material and Methods: Forty breast lesions were prospectively examined with dynamic MR and power Doppler US. Time-signal intensity curves of enhancement were obtained for both methods. The shape of the curve was analyzed to be benign, indeterminate or malignant. The curves were also analyzed quantitatively by calculating the slope of the curve and the area under the curve (both methods), relative enhancement (MR), and time to peak (US). The lesions were divided into malignant lesions, fibroadenomas, and other benign lesions. The results were compared to histology. Results: In the subjective analysis of the MR curve in differentiating between benign and malignant lesions the accuracy was 90%. The MR curve also enabled differentiation between fibroadenomas and malignancies. The accuracy of the US curve was 38%. Quantitatively, statistically significant differences were found using all the MR variables, except between malignancies and fibroadenomas. Using the US variables, no significant difference was found between the groups. Conclusion: The dynamics of contrast-enhanced MR were reliable in the differential diagnosis of solid breast lesions, but contrast-enhanced power Doppler US was of limited value.

MR imaging contrast enhancement based on intermolecular zero quantum coherences.

A new method for magnetic resonance imaging (MRI) based on the detection of relatively strong signal from intermolecular zero-quantum coherences (iZQCs) is reported. Such a signal would not be observable in the conventional framework of magnetic resonance; it originates in long-range dipolar couplings (10 micrometers to 1 millimeter) that are traditionally ignored. Unlike conventional MRI, where image contrast is based on variations in spin density and relaxation times (often with injected contrast agents), contrast with iZQC images comes from variations in the susceptibility over a distance dictated by gradient strength. Phantom and in vivo (rat brain) data confirm that iZQC images give contrast enhancement. This contrast might be useful in the detection of small tumors, in that susceptibility correlates with oxygen concentration and in functional MRI.

Safety, Tolerance, and Pharmacokinetics of High Doses of Gadodiamide Injection, a Nonionic Magnetic Resonance Imaging Contrast Agent

Rationale and Objectives. Doses of up to 0.3 mmol/kg of gadodiamide injection have been used clinically to provide contrast enhancement in MR imaging of the central nervous system. This double-blind study evaluated the safety, tolerance, and pliarmacokinetics of gadodiamide doses of 0.5–1.5 mmol/kg administered intravenously. Methods. Groups of seven healthy adults were assigned randomly to receive either a placebo (two subjects per group) or one of five ascending doses (0.5, 0.75, 1.0, 1.25, or 1.5 mmol/kg) of gadodiamide (five subjects per group). Results. The frequencies of adverse events and injection-associated discomfort, all of which were nonserious, were statistically similar for gadodiamide and placebo subjects. Flushing occurred more frequently in those subjects having received gadodiamide. No clinically significant effects on vital signs or laboratory values were observed. Gadodiamide was rapidly eliminated from the serum (half-life of approximately 2 hr) and exhibited linear pharmacokinedcs. Nearly the entire dose was recovered in the urine as unmetabolized gadodiamide. Conclusion. Gadodiamide doses of 0.5–1.5 mmol/kg were safe and well tolerated in healthy adults, with no dose-related trends observed in adverse events or other safety parameters. The pharmacokinetics were consistent with those observed for lower doses. Rationale and Objectives. Doses of up to 0.3 mmol/kg of gadodiamide injection have been used clinically to provide contrast enhancement in MR imaging of the central nervous system. This double-blind study evaluated the safety, tolerance, and pliarmacokinetics of gadodiamide doses of 0.5–1.5 mmol/kg administered intravenously. Methods. Groups of seven healthy adults were assigned randomly to receive either a placebo (two subjects per group) or one of five ascending doses (0.5, 0.75, 1.0, 1.25, or 1.5 mmol/kg) of gadodiamide (five subjects per group). Results. The frequencies of adverse events and injection-associated discomfort, all of which were nonserious, were statistically similar for gadodiamide and placebo subjects. Flushing occurred more frequently in those subjects having received gadodiamide. No clinically significant effects on vital signs or laboratory values were observed. Gadodiamide was rapidly eliminated from the serum (half-life of approximately 2 hr) and exhibited linear pharmacokinedcs. Nearly the entire dose was recovered in the urine as unmetabolized gadodiamide. Conclusion. Gadodiamide doses of 0.5–1.5 mmol/kg were safe and well tolerated in healthy adults, with no dose-related trends observed in adverse events or other safety parameters. The pharmacokinetics were consistent with those observed for lower doses.