Thursday, April 4, 2019

Investigative Radiology,https://journals.lww.com/investigativeradiology/pages/default.aspx

7 T Magnetic Resonance Spectroscopic Imaging in Multiple Sclerosis: How ...
7 T Magnetic Resonance Spectroscopic Imaging in Multiple Sclerosis: How Does Spatial Resolution Affect the Detectability of...
Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the...
Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted
Reduction of Metal Artifacts and Improvement in Dose Efficiency Using...
Reduction of Metal Artifacts and Improvement in Dose Efficiency Using Photon-Counting Detector Computed Tomography and Tin...
April 2019: Val M. Runge, MD, a note from the Editor
This issue of the journal, as always, has many outstanding articles, representing cutting edge research and technology in diagnostic imaging. A study at 7 T demonstrates the utility at that field strength for increased spatial resolution in spectroscopy for the evaluation of multiple sclerosis lesions. A second excellent article explores visualization of the glymphatic system (CSF microcirculation) on MR following IV administration of gadolinium-based contrast agents. A third article describes advances in reduction of metal artifacts and improvement in dose efficiency using photon-counting detector CT in combination with tin filtration. The remaining papers explore important advances in tomoelastography, prostate imaging (specifically DWI), and T1- and T2*-mapping, as well as assessing robustness and reproducibility in Radiomics and adverse events with gadolinium chelate administration.
Current Issue Highlights
 Collapse Box Original Articles
A Structured Survey on Adverse Events Occurring Within 24 Hours After Intravenous Exposure to Gadodiamide or Gadoterate Meglumine: A Controlled Prospective Comparison Study
Parillo, Marco; Sapienza, Martina; Arpaia, Francesco; More
Investigative Radiology. 54(4):191-197, April 2019.

Abstract
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Abstract:
Objective
This study compares the incidence of new-onset symptoms within 24 hours after enhanced magnetic resonance imaging (eMRI) with intravenous administration of gadodiamide or gadoterate meglumine compared with a control group undergoing unenhanced MRI (uMRI).

Materials and Methods
A prospective cohort study (n = 1088 patients) was designed to assess the incidence of symptoms within 24 hours after administration of gadodiamide or gadoterate meglumine. The participants underwent a structured questionnaire by phone call before and 24 hours after the MRI scan to check for symptoms that were not present before the scan. The questionnaire included a list of active questions aimed to test the prevalence of symptoms that have been proposed in the debated definition of gadolinium deposition disease (GDD) and that we recorded in this study as GDD-like. In particular, the following symptoms and signs were tested: central torso pain, arm or leg pain, bone pain, headache, skin redness (any site of the body), fatigue, and mental confusion.

Fisher exact test was used to test differences between groups with significance threshold set at P < 0.05.

Results
Within the 24 hours after the MRI scan, 8.3% of patients reported at least one new-onset symptom in the uMRI group versus 17.4% in the gadodiamide eMRI versus 17.8% in the gadoterate meglumine eMRI group. The difference between the eMRI and the uMRI group was statistically significant ( P < 0.001 for gadodiamide and P < 0.001 for gadoterate meglumine). There was not a different incidence of symptoms between the gadodiamide and the gadoterate meglumine eMRI groups. For gadodiamide, fatigue ( P < 0.05) and dizziness ( P < 0.05) were symptoms significantly more frequent than uMRI group; for gadoterate meglumine, fatigue ( P < 0.01), mental confusion ( P < 0.01), and diarrhea ( P < 0.01) were significantly more frequent than uMRI group.

Conclusions
We found that the onset of new symptoms within 24 hours after exposure to gadolinium-based contrast agent was more frequent than after uMRI. Among GDD-like symptoms, fatigue and mental confusion were the most frequent symptoms reported after eMRI. The other GDD-like symptoms were not overreported after eMRI versus uMRI. Thus, these results are questioning the term GDD.

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Tomoelastography for the Evaluation of Pediatric Nonalcoholic Fatty Liver Disease
Hudert, Christian A.; Tzschätzsch, Heiko; Rudolph, Birgit; More
Investigative Radiology. 54(4):198-203, April 2019.

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Objectives
Today, nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adults alike. Yet, the noninvasive evaluation of disease severity remains a diagnostic challenge. In this study, we apply multifrequency magnetic resonance elastography (mMRE) for the quantification of liver steatosis and fibrosis in adolescents with NAFLD.

Methods
Fifty adolescents (age range, 10–17 years; mean BMI, 33.9 kg/m 2 ; range, 21.4–42.1 kg/m 2 ) with biopsy-proven NAFLD were included in this prospective study. Multifrequency magnetic resonance elastography was performed using external multifrequency vibrations of 30 to 60 Hz and tomoelastography postprocessing, resulting in penetration rate ( a ) and shear wave speed ( c ). Hepatic fat fraction was determined using Dixon method. The diagnostic accuracy of mMRE in grading liver steatosis and staging liver fibrosis was assessed by receiver operating characteristic curve analysis.

Results
Multifrequency magnetic resonance elastography parameters c and a were independently sensitive to fibrosis and steatosis, respectively, providing area under the receiver operating characteristic values of 0.79 (95% confidence interval [CI], 0.66–0.92), 0.91 (95% CI, 0.83–0.99), and 0.90 (95% CI, 0.80–0.99) for the detection of any (≥F1), moderate (≥F2), and advanced (≥F3) fibrosis, and 0.87 (95% CI, 0.76–0.97) and 0.87 (95% CI, 0.77–0.96) for the detection of moderate (≥S2) and severe (S3) steatosis.

Conclusions
One mMRE measurement provides 2 independent parameters with very good diagnostic accuracy in detecting moderate and advanced fibrosis as well as moderate and severe steatosis in pediatric NAFLD.

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SDC
Reduction of Metal Artifacts and Improvement in Dose Efficiency Using Photon-Counting Detector Computed Tomography and Tin Filtration
Zhou, Wei; Bartlett, David J.; Diehn, Felix E.; More
Investigative Radiology. 54(4):204-211, April 2019.

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Objectives
The aim of this study was to investigate the impact on metal artifacts and dose efficiency of using a tin filter in combination with high-energy threshold (TH) images of a photon-counting detector (PCD) computed tomography (CT) system.

Materials and Methods
A 3D-printed spine with pedicle screws was scanned on a PCD-CT system with and without tin filtration. Image noise and severity of artifacts were measured for low-energy threshold (TL) and TH images. In a prospective, institutional review board–approved, Health Insurance Portability and Accountability Act-compliant study, 20 patients having a clinical energy-integrating detector (EID) CT were scanned on a PCD-CT system using tin filtration. Images were reviewed by 3 radiologists to evaluate visualization of anatomic structures, diagnostic confidence, and image preference. Artifact severity and image noise were measured. Wilcoxon signed rank was used to test differences between PCD-CT TH and EID-CT images.

Results
Phantom TH images with tin filtration reduced metal artifacts and had comparable noise (32 HU) to TL images (29 HU) acquired without tin filtration. Visualization scores for the cortex, trabeculae, and implant-trabecular interface from PCD-CT TH images (4.4 ± 0.9, 4.4 ± 1.0, and 4.4 ± 1.0) were significantly higher ( P < 0.0001) than EID-CT images (3.3 ± 1.3, 3.3 ± 1.2, and 3.3 ± 1.6). A strong preference was shown for PCD-CT TH images due to improved diagnostic confidence and decreased artifact severity. Noise in PCD-CT TH images (93 ± 41 HU) was significantly lower than that in EID-CT images (133 ± 92 HU, P < 0.05).

Conclusions
Threshold high images acquired with tin filtration on PCD-CT demonstrated a substantial decrease in metal artifacts and an increase in dose efficiency compared with EID-CT.

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SDC
T1- and T2*-Mapping for Assessment of Tendon Tissue Biophysical Properties: A Phantom MRI Study
Bachmann, Elias; Rosskopf, Andrea B.; Götschi, Tobias; More
Investigative Radiology. 54(4):212-220, April 2019.

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Objectives
The aim of this study was to quantitatively assess changes in collagen structure using MR T1- and T2*-mapping in a novel controlled ex vivo tendon model setup.

Materials and Methods
Twenty-four cadaveric bovine flexor tendons underwent MRI at 3 T before and after chemical modifications, representing mechanical degeneration and augmentation. Collagen degradation (COL), augmenting collagen fiber cross-linking (CXL), and a control (phosphate-buffered saline [PBS]) were examined in experimental groups, using histopathology as standard of reference. Variable echo-time and variable-flip angle gradient-echo sequences were used for T2*- and T1-mapping, respectively. Standard T1- and T2-weighted spin-echo sequences were acquired for visual assessment of tendon texture. Tendons were assessed subsequently for their biomechanical properties and compared with quantitative MRI analysis.

Results
T1- and T2*-mapping was feasible and repeatable for untreated (mean, 545 milliseconds, 2.0 milliseconds) and treated tendons. Mean T1 and T2* values of COL, CXL, and PBS tendons were 1459, 934, and 1017 milliseconds, and 5.5, 3.6, and 2.5 milliseconds, respectively. T2* values were significantly different between enzymatically degraded tendons, cross-linked tendons, and controls, and were significantly correlated with mechanical tendon properties ( r = −0.74, P < 0.01). T1 values and visual assessment could not differentiate CXL from PBS tendons. Photo-spectroscopy showed increased autofluorescence of cross-linked tendons, whereas histopathology verified degenerative lesions of enzymatically degraded tendons.

Conclusions
T2*-mapping has the potential to detect and quantify subtle changes in tendon collagen structure not visible on conventional clinical MRI. Tendon T2* values might serve as a biomarker for biochemical alterations associated with tendon pathology.

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Robustness and Reproducibility of Radiomics in Magnetic Resonance Imaging: A Phantom Study
Baeßler, Bettina; Weiss, Kilian; Pinto dos Santos, Daniel
Investigative Radiology. 54(4):221-228, April 2019.

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Abstract:
Objectives
The aim of this study was to investigate the robustness and reproducibility of radiomic features in different magnetic resonance imaging sequences.

Materials and Methods
A phantom was scanned on a clinical 3 T system using fluid-attenuated inversion recovery (FLAIR), T1-weighted (T1w), and T2-weighted (T2w) sequences with low and high matrix size. For retest data, scans were repeated after repositioning of the phantom. Test and retest datasets were segmented using a semiautomated approach. Intraobserver and interobserver comparison was performed. Radiomic features were extracted after standardized preprocessing of images. Test-retest robustness was assessed using concordance correlation coefficients, dynamic range, and Bland-Altman analyses. Reproducibility was assessed by intraclass correlation coefficients.

Results
The number of robust features (concordance correlation coefficient and dynamic range ≥ 0.90) was higher for features calculated from FLAIR than from T1w and T2w images. High-resolution FLAIR images provided the highest percentage of robust features (n = 37/45, 81%). No considerable difference in the number of robust features was observed between low- and high-resolution T1w and T2w images (T1w low: n = 26/45, 56%; T1w high: n = 25/45, 54%; T2 low: n = 21/45, 46%; T2 high: n = 24/45, 52%). A total of 15 (33%) of 45 features showed excellent robustness across all sequences and demonstrated excellent intraobserver and interobserver reproducibility (intraclass correlation coefficient ≥ 0.75).

Conclusions
FLAIR delivers the most robust substrate for radiomic analyses. Only 15 of 45 features showed excellent robustness and reproducibility across all sequences. Care must be taken in the interpretation of clinical studies using nonrobust features.

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SDC
Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted
Deike-Hofmann, Katerina; Reuter, Julia; Haase, Robert; More
Investigative Radiology. 54(4):229-237, April 2019.

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Background
The "glymphatic system" (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies a pathway through and out of the central nervous system (CNS); malfunction of the system is implicated in a variety of neurological disorders. In this exploratory study, we analyzed the potential of a new imaging approach that we coined delayed T2-weighted gadolinium-enhanced imaging to visualize the GS in vivo.

Methods
Heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) magnetic resonance imaging was obtained before, and 3 hours and 24 hours after intravenous gadolinium-based contrast agent (GBCA) application in 33 neurologically healthy patients and 7 patients with an impaired blood-brain barrier (BBB) due to cerebral metastases. Signal intensity (SI) was determined in various cerebral fluid spaces, and white matter hyperintensities were quantified by applying the Fazekas scoring system.

Findings
Delayed hT2w-FLAIR showed GBCA entry into the CNS via the choroid plexus and the ciliary body, with GBCA drainage along perineural sheaths of cranial nerves and along perivascular spaces of penetrating cortical arteries. In all patients and all sites, a significant SI increase was found for the 3 hours and 24 hours time points compared with baseline. Although no significant difference in SI was found between neurologically healthy patients and patients with an impaired BBB, a significant positive correlation between Fazekas scoring system and SI increase in the perivascular spaces 3 hours post injection was shown.

Interpretation
Delayed T2-weighted gadolinium-enhanced imaging can visualize the GBCA pathway into and through the GS. Presence of GBCAs within the GS might be regarded as part of the natural excretion process and should not be mixed up with gadolinium deposition. Rather, the correlation found between deep white matter hyperintensities, an imaging sign of vascular dementia, and GS functioning demonstrated feasibility to exploit the pathway of GBCAs through the GS for diagnostic purposes.

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Accelerated Segmented Diffusion-Weighted Prostate Imaging for Higher Resolution, Higher Geometric Fidelity, and Multi-b Perfusion Estimation
Aksit Ciris, Pelin; Chiou, Jr-yuan George; Glazer, Daniel I.; More
Investigative Radiology. 54(4):238-246, April 2019.

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Abstract:
Purpose
The aim of this study was to improve the geometric fidelity and spatial resolution of multi-b diffusion-weighted magnetic resonance imaging of the prostate.

Materials and Methods
An accelerated segmented diffusion imaging sequence was developed and evaluated in 25 patients undergoing multiparametric magnetic resonance imaging examinations of the prostate. A reduced field of view was acquired using an endorectal coil. The number of sampled diffusion weightings, or b -factors, was increased to allow estimation of tissue perfusion based on the intravoxel incoherent motion (IVIM) model. Apparent diffusion coefficients measured with the proposed segmented method were compared with those obtained with conventional single-shot echo-planar imaging (EPI).

Results
Compared with single-shot EPI, the segmented method resulted in faster acquisition with 2-fold improvement in spatial resolution and a greater than 3-fold improvement in geometric fidelity. Apparent diffusion coefficient values measured with the novel sequence demonstrated excellent agreement with those obtained from the conventional scan ( R 2 = 0.91 for b max = 500 s/mm 2 and R 2 = 0.89 for b max = 1400 s/mm 2 ). The IVIM perfusion fraction was 4.0% ± 2.7% for normal peripheral zone, 6.6% ± 3.6% for normal transition zone, and 4.4% ± 2.9% for suspected tumor lesions.

Conclusions
The proposed accelerated segmented prostate diffusion imaging sequence achieved improvements in both spatial resolution and geometric fidelity, along with concurrent quantification of IVIM perfusion.

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Table of Contents Outline | Back to Top
 Collapse Box Technical Note
7 T Magnetic Resonance Spectroscopic Imaging in Multiple Sclerosis: How Does Spatial Resolution Affect the Detectability of Metabolic Changes in Brain Lesions?
Heckova, Eva; Strasser, Bernhard; Hangel, Gilbert J.; More
Investigative Radiology. 54(4):247-254, April 2019.

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Objectives
The aim of this study was to assess the utility of increased spatial resolution of magnetic resonance spectroscopic imaging (MRSI) at 7 T for the detection of neurochemical changes in multiple sclerosis (MS)–related brain lesions.

Materials and Methods
This prospective, institutional review board–approved study was performed in 20 relapsing-remitting MS patients (9 women/11 men; mean age ± standard deviation, 30.8 ± 7.7 years) after receiving written informed consent. Metabolic patterns in MS lesions were compared at 3 different spatial resolutions of free induction decay MRSI with implemented parallel imaging acceleration: 2.2 × 2.2 × 8 mm 3 ; 3.4 × 3.4 × 8 mm 3 ; and 6.8 × 6.8 × 8 mm 3 voxel volumes, that is, matrix sizes of 100 × 100, 64 × 64, and 32 × 32, respectively. The quality of data was assessed by signal-to-noise ratio and Cramér-Rao lower bounds. Statistical analysis was performed using Wilcoxon signed-rank tests with correction for multiple testing.

Results
Seventy-seven T2-hyperintense MS lesions were investigated (median volume, 155.7 mm 3 ; range, 10.8–747.0 mm 3 ). The mean metabolic ratios in lesions differed significantly between the 3 MRSI resolutions (ie, 100 × 100 vs 64 × 64, 100 × 100 vs 32 × 32, and 64 × 64 vs 32 × 32; P < 0.001). With the ultra-high resolution (100 × 100), we obtained 40% to 80% higher mean metabolic ratios and 100% to 150% increase in maximum metabolic ratios in the MS lesions compared with the lowest resolution (32 × 32), while maintaining good spectral quality (signal-to-noise ratio >12, Cramér-Rao lower bounds <20%) and measurement time of 6 minutes. There were 83% of MS lesions that showed increased myo -inositol/ N -acetylaspartate with the 100 × 100 resolution, but only 66% were distinguishable with the 64 × 64 resolution and 35% with the 32 × 32 resolution.

Conclusions
Ultra-high-resolution MRSI (~2 × 2 × 8 mm 3 voxel volume) can detect metabolic alterations in MS, which cannot be recognized by conventional MRSI resolutions, within clinically acceptable time.

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SDC
Table of Contents Outline | Back to Top
 Collapse Box Erratum
Rapid Diffusion-Weighted Magnetic Resonance Imaging of the Brain Without Susceptibility Artifacts: Single-Shot STEAM With Radial Undersampling and Iterative Reconstruction: Erratum
Investigative Radiology. 54(4):255, April 2019.

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