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Investigative Radiology - Current Issue

Investigative Radiology - Current Issue
  1. Comparison of Unenhanced T1-Weighted Signal Intensities Within the Dentate Nucleus and the Globus Pallidus After Serial Applications of Gadopentetate Dimeglumine Versus Gadobutrol in a Pediatric Population
    imageObjective The aim of this study was to evaluate and compare changes in T1-weighted signal intensity (SI) within the dentate nucleus (DN) and globus pallidus (GP) in a pediatric population after serial applications of the linear gadolinium-based magnetic resonance contrast medium gadopentetate dimeglumine and the more stable macrocyclic agent gadobutrol. Materials and Methods Institutional review board approval was obtained. Two similar pediatric patient cohorts who underwent at least 3 serial contrast-enhanced magnetic resonance imaging (MRI) examinations with sole application of gadopentetate dimeglumine or gadobutrol were analyzed. All MRI examinations were performed on a 1.5 T system acquiring unenhanced T1-weighted spin echo sequences, which were evaluated on the baseline MRI and after the contrast medium administrations. For analysis of SI changes in the DN, the ratios of the DN to the pons (P) and to the middle cerebellar peduncle (MCP) were assessed. The GP was compared with the thalamus (TH) by dividing the SIs between GP and TH (GP-to-TH ratio). Results Twenty-eight patients (13 boys, 15 girls; mean age, 8.4 ± 6.8 years) who received at least 3 applications of gadopentetate dimeglumine and 25 patients (13 boys, 12 girls; mean age, 9.7 ± 5.4 years) with 3 or more gadobutrol injections were included. After 3 administrations of gadopentetate dimeglumine, the T1-weighted SI ratios significantly increased: mean difference value of 0.036 ± 0.031 (DN-to-P; P < 0.001), 0.034 ± 0.032 (DN-to-MCP; P < 0.001), and 0.025 ± 0.025 (GP-to-TH; P = 0.001). In a subanalysis of 12 patients with more than 3 injections of gadopentetate dimeglumine, the mean differences of the SI ratios were slightly higher: 0.043 ± 0.032 (DN-to-P; P = 0.001), 0.041 ± 0.035 (DN-to-MCP; P = 0.002), and 0.028 ± 0.025 (GP-to-TH; P = 0.003). In contrast, gadobutrol did not show a significant influence on the SI ratios, neither after 3 nor after more than 3 applications. Conclusions The T1-weighted SI increase within the DN and GP after serial administrations of the linear contrast medium gadopentetate dimeglumine, but not after serial applications of the macrocyclic agent gadobutrol, found in a pediatric population, is consistent with results published for adult patients. The clinical impact of the intracranial T1-hyperintensities is currently unclear. However, in accordance with the recent decision of the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency, intravenous macrocyclic agents should be preferred and MR contrast media should be used with caution and awareness of the pediatric brain development in children and adolescents.



  2. A Pharmacokinetics, Efficacy, and Safety Study of Gadoterate Meglumine in Pediatric Subjects Aged Younger Than 2 Years
    imageObjectives The primary objective of this study was to investigate the pharmacokinetic profile of gadoterate meglumine in pediatric patients younger than 2 years; the secondary objectives were to document its efficacy and safety. Material and Methods This was a Phase IV open-label, prospective study conducted in 9 centers (4 countries). Forty-five patients younger than 2 years with normal estimated glomerular filtration rate and scheduled to undergo routine gadolinium-enhanced magnetic resonance imaging (MRI) of any organ were included and received a single intravenous injection of gadoterate meglumine (0.1 mmol/kg). To perform the population pharmacokinetics analysis, 3 blood samples per subject were drawn during 3 time windows at time points allocated by randomization. Results Gadoterate meglumine concentrations were best fitted using a 2-compartmental model with linear elimination from central compartment. The median total clearance adjusted to body weight was estimated at 0.06 L/h per kg and increased with estimated glomerular filtration rate according to a power model. The median volume of distribution at steady state (Vss) adjusted to body weight was estimated at 0.047 L/kg. Estimated median terminal half-life (t1/2β) was 1.35 h, and the median systemic exposure (area under the curve) was 1591 μmol h/L. Efficacy was assessed by comparing precontrast +postcontrast images to precontrast images in a subset of 28 subjects who underwent an MRI examination of brain, spine, and associated tissues. A total of 28 lesions were identified and analyzed in 15 subjects with precontrast images versus 30 lesions in 16 subjects with precontrast + postcontrast images. Lesion visualization was improved with a mean (SD) increase in scores at subject level of 0.7 (1.0) for lesion border delineation, 0.9 (1.6) for internal morphology, and 3.1 (3.2) for contrast enhancement. Twenty-six adverse events occurred postinjection in 13 subjects (28.9%), including 3 serious reported in 1 subject (2.2%). One subject (2.2%) experienced 1 rash of moderate intensity considered as related to gadoterate meglumine. Conclusions The pharmacokinetic profile of gadoterate meglumine after a single intravenous injection of 0.1 mmol/kg was appropriately described in newborns and infants younger than 2 years, for whom no dose adjustment is required. The improved efficacy of gadoterate meglumine for contrast-enhanced MRI examination of brain, spine, and associated tissues, as well as its good safety profile, was also demonstrated in this population.



  3. Heavily Calcified Coronary Arteries: Advanced Calcium Subtraction Improves Luminal Visualization and Diagnostic Confidence in Dual-Energy Coronary Computed Tomography Angiography
    imageObjectives The aim of this study was to evaluate a prototype dual-energy computed tomography calcium subtraction algorithm and its impact on luminal visualization in patients with heavily calcified coronary arteries. Materials and Methods Twenty-nine patients (62% male; mean age, 64 ± 7 years) who had undergone dual-energy coronary computed tomography angiography were retrospectively included in this institutional review board–approved, Health Insurance Portability and Accountability Act–compliant study. Linearly blended (M_0.6) and calcium-subtracted images were reconstructed. Two independent observers assessed luminal visualization of the coronary arteries in a segment-based analysis, subjective image quality, and diagnostic confidence using 5-point Likert scales. Contrast-to-noise ratios for both data sets were calculated. Wilcoxon testing and Cohen's κ were used for statistical comparisons. Results Calcium-subtracted image series showed improved lumen visualization of the coronary arteries (P = 0.008), with excellent interreader agreement (mean score, 3.3; κ = 0.82), compared with M_0.6 series (mean score, 2.9; κ = 0.77). The calcium subtraction algorithm improved diagnostic confidence compared with the M_0.6 reconstructions (mean scores, 4.0 and 3.1, respectively; all P ≤ 0.002). The image quality analysis showed no significant differences between calcium-subtracted and M_0.6 data sets (subjectively: mean scores, 4.1 and 4.2, respectively, P = 0.442; objectively: mean contrast-to-noise ratio, 37.0 and 38.2, respectively, P = 0.733). Conclusions A prototype algorithm for calcium subtraction improves coronary lumen visualization and diagnostic confidence in patients with heavy coronary calcifications without differences in conventional subjective and objective measures of image quality.



  4. Non contrast, Pseudo-Continuous Arterial Spin Labeling and Accelerated 3-Dimensional Radial Acquisition Intracranial 3-Dimensional Magnetic Resonance Angiography for the Detection and Classification of Intracranial Arteriovenous Shunts
    imageObjectives The aim of this study was to assess the sensitivity and specificity of pseudo-continuous arterial spin labeling (PCASL) magnetic resonance angiography (MRA) with 3-dimensional (3D) radial acquisition for the detection of intracranial arteriovenous (AV) shunts. Materials and Methods A total of 32 patients who underwent PCASL-MRA, clinical magnetic resonance imaging (MRI)/MRA exam, and digital subtraction angiography (DSA) were included in this retrospective analysis. Twelve patients presented with AV shunts. Among these were 8 patients with AV malformations (AVM) and 4 patients with AV fistulas (AVF). The clinical MRI/MRA included 3D time-of-flight MRA in all cases and time-resolved, contrast-enhanced MRA in 9 cases (6 cases with AV shunting). Research MRI and clinical MRI were independently evaluated by 2 neuroradiologists blinded to patient history. A third radiologist evaluated DSA imaging. A diagnostic confidence score was used for the presence of abnormalities associated with AV shunting (1–5). The AVMs were characterized using the Spetzler-Martin scale, whereas AVFs were characterized using the Borden classification. κ Statistics were applied to assess intermodality agreement. Results Compared with clinical MRA, noncontrast PCASL-MRA with 3D radial acquisition yielded excellent sensitivity and specificity for the detection of intracranial AV shunts (reader 1: 100%/100%, clinical MRA: 91.7%, 94.4%; reader 2: 91.7%/100%, clinical MRA: 91.7%/100%). Diagnostic confidence was 4.8/4.66 with PCASL-MRA and 4.25/4.66 with clinical MRA. For AVM characterization with PCASL-MRA, intermodality agreement with DSA showed κ values of 0.43 and 0.6 for readers 1 and 2, respectively. For AVF characterization, intermodality agreement showed κ values of 0.56 for both readers. Conclusion Noncontrast PCASL-MRA with 3D radial acquisition is a potential tool for the detection and characterization of intracranial AV shunts with a sensitivity and specificity equivalent or higher than routine clinical MRA.



  5. Unenhanced Dual-Energy Computed Tomography: Visualization of Brain Edema
    imagePurpose The aim of this study was to determine whether dual-energy computed tomography (DECT) imaging is superior to conventional noncontrast computed tomography (CT) imaging for the detection of acute ischemic stroke. Materials and Methods This was a retrospective, single-center study of 40 patients who presented to the emergency department (ED) of a major, acute care, teaching center with signs and symptoms of acute stroke. Only those patients who presented to the ED within 4 hours of symptom onset were included in this study. All 40 patients received a noncontrast DECT of the head at the time of presentation. Each patient also received standard noncontrast CT of the head 24 hours after their initial presentation to the ED. “Brain edema” images were then reconstructed using 3-material decomposition with parameters adjusted to suppress gray/white matter contrast while preserving edema and increasing its conspicuity. The initial unenhanced, mixed images, brain edema, and 24-hour follow-up true noncontrast (TNC) images were reviewed and assigned Alberta Stroke Program Early CT scores. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results Of the 40 patients, 28 (70%) were diagnosed with an acute infarction. Brain edema reconstructions were better able to predict end infarction volume, with Alberta Stroke Program Early CT scores similar to the 24-hour follow-up TNC CT (7.75 vs 7.7; P > 0.05), whereas the mixed images routinely underestimated the extent of infarction (8.975 vs 7.7; P < 0.001). Initial TNC images had a sensitivity, specificity, PPV, and NPV of 80% (95% confidence interval [CI], 51.9%–95.7%), 72.7% (95% CI, 39%–94%), 80% (95% CI, 51.9%–95.7%), and 72.73% (95% CI, 51.91%–95.67%), respectively. The DECT brain edema images provided a sensitivity, specificity, PPV, and NPV of 93.33% (95% CI, 68.05%–99.83%), 100% (95% CI, 71.51%–100%), 100% (95% CI, 76.84%–100%), and 91.67% (95% CI, 61.52%–99.79%), respectively. There was very good interrater reliability across all 3 imaging techniques. Conclusion Brain edema reconstructions are able to more accurately detect edema and end-infarct volume as compared with initial TNC images. This provides a better assessment of the degree and extent of infarction and may serve to better guide therapy in the future.


  6. Quantitative Proton Spectroscopy of the Testes at 3 T: Toward a Noninvasive Biomarker of Spermatogenesis
    imageObjectives The aim of this study was to compare testicular metabolite concentrations between fertile control subjects and infertile men. Materials and Methods Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed in the testes with and without water suppression at 3 T in 9 fertile control subjects and 9 infertile patients (8 with azoospermia and 1 with oligospermia). In controls only, the T1 and T2 values of water and metabolites were also measured. Absolute metabolite concentrations were calculated using the unsuppressed water signal as a reference and correcting for the relative T1 and T2 weighting of the water and metabolite signals. Results Testicular T1 values of water, total choline, and total creatine were 2028 ± 125 milliseconds, 1164 ± 105 milliseconds, and 1421 ± 314 milliseconds, respectively (mean ± standard deviation). T2 values were 154 ± 11 milliseconds, 342 ± 53 milliseconds, and 285 ± 167 milliseconds, respectively. Total choline concentration was lower in patients (mean, 1.5 mmol/L; range, 0.9–2.1 mmol/L) than controls (mean, 4.4 mmol/L; range, 3.2–5.7 mmol/L; P = 4 × 10−5). Total creatine concentration was likewise reduced in patients (mean, 1.1 mmol/L; range, undetectable −2.7 mmol/L) compared with controls (mean, 3.6 mmol/L; range, 2.5–4.7 mmol/L; P = 1.6 × 10−4). The myo-inositol signal normalized to the water reference was also lower in patients than controls (P = 4 × 10−5). Conclusions Testicular metabolite concentrations, measured by proton spectroscopy at 3 T, may be valuable as noninvasive biomarkers of spermatogenesis.



  7. The Effect of Perinatal Gadolinium-Based Contrast Agents on Adult Mice Behavior
    imageObjectives The aim of this study was to examine the effects of perinatal exposure to gadolinium (Gd)-based contrast agents (GBCAs) on the behavior of adulthood offspring. Materials and Methods Pregnant Balb/C mice (n = 5 per group) were intravenously injected with gadoterate meglumine (Magnescope, macrocyclic GBCA), gadodiamide (Omniscan, linear GBCA), or vehicle from pregnancy day 15 to 19, corresponding to embryonic day 15 to 19 of the fetus, at 2 mmol/kg body weight per day. Brain samples from dams and pups were collected on postpartum day 28. The total Gd concentration was quantified by inductively coupled plasma-mass spectrometry (dams, n = 3; gadoterate meglumine-treated pups group, n = 9; and gadodiamide-treated pups group, n = 10). Behavioral testing of offspring was started on postpartum day 70 (control group, n = 22; gadoterate meglumine-treated group, n = 23; and gadodiamide-treated group, n = 20). Results Higher levels of Gd retention were observed in dams and pups in the gadodiamide-treated group. Perinatal exposure to GBCAs caused anxiety-like behavior, disrupted motor coordination, impaired memory function, stimulated tactile sensitivity, and decreased muscle strength, particularly in the gadodiamide-treated group. Conclusions In the present study, we showed that Gd was transferred to pups and was retained in their brain during postnatal development. Gadolinium retention may lead to impaired brain development. These findings indicate that the use of GBCAs in pregnant women should be avoided because it may have adverse effects on the fetus, particularly on brain development.



  8. Multiparametric Magnetic Resonance Imaging of Prostate Cancer Bone Disease: Correlation With Bone Biopsy Histological and Molecular Features
    imageObjectives The aim of this study was to correlate magnetic resonance imaging (MRI) of castration-resistant prostate cancer (CRPC) bone metastases with histological and molecular features of bone metastases. Materials and Methods Forty-three bone marrow biopsies from 33 metastatic CRPC (mCRPC) patients with multiparametric MRI and documented bone metastases were evaluated. A second cohort included 10 CRPC patients with no bone metastases. Associations of apparent diffusion coefficient (ADC), normalized b900 diffusion-weighted imaging (nDWI) signal, and signal-weighted fat fraction (swFF) with bone marrow biopsy histological parameters were evaluated using Mann-Whitney U test and Spearman correlations. Univariate and multivariate logistic regression models were analyzed. Results Median ADC and nDWI signal was significantly higher, and median swFF was significantly lower, in bone metastases than nonmetastatic bone (P < 0.001). In the metastatic cohort, 31 (72.1%) of 43 biopsies had detectable cancer cells. Median ADC and swFF were significantly lower and median nDWI signal was significantly higher in biopsies with tumor cells versus nondetectable tumor cells (898 × 10−6 mm2/s vs 1617 × 10−6 mm2/s; 11.5% vs 62%; 5.3 vs 2.3, respectively; P < 0.001). Tumor cellularity inversely correlated with ADC and swFF, and positively correlated with nDWI signal (P < 0.001). In serial biopsies, taken before and after treatment, changes in multiparametric MRI parameters paralleled histological changes. Conclusions Multiparametric MRI provides valuable information about mCRPC bone metastases. These data further clinically qualify DWI as a response biomarker in mCRPC.



  9. Contrast Media Research 2017 Durango, Colorado USA, October 22–25, 2017 Convener: Michael F. Tweedle, PhD Erratum
    No abstract available



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