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20 pages, 4029 KiB  
Study Protocol
Four-Dimensional Flow MRI for Cardiovascular Evaluation (4DCarE): A Prospective Non-Inferiority Study of a Rapid Cardiac MRI Exam: Study Protocol and Pilot Analysis
by Jiaxing Jason Qin, Mustafa Gok, Alireza Gholipour, Jordan LoPilato, Max Kirkby, Christopher Poole, Paul Smith, Rominder Grover and Stuart M. Grieve
Diagnostics 2024, 14(22), 2590; https://doi.org/10.3390/diagnostics14222590 - 18 Nov 2024
Viewed by 785
Abstract
Background: Accurate measurements of flow and ventricular volume and function are critical for clinical decision-making in cardiovascular medicine. Cardiac magnetic resonance (CMR) is the current gold standard for ventricular functional evaluation but is relatively expensive and time-consuming, thus limiting the scale of clinical [...] Read more.
Background: Accurate measurements of flow and ventricular volume and function are critical for clinical decision-making in cardiovascular medicine. Cardiac magnetic resonance (CMR) is the current gold standard for ventricular functional evaluation but is relatively expensive and time-consuming, thus limiting the scale of clinical applications. New volumetric acquisition techniques, such as four-dimensional flow (4D-flow) and three-dimensional volumetric cine (3D-cine) MRI, could potentially reduce acquisition time without loss in accuracy; however, this has not been formally tested on a large scale. Methods: 4DCarE (4D-flow MRI for cardiovascular evaluation) is a prospective, multi-centre study designed to test the non-inferiority of a compressed 20 min exam based on volumetric CMR compared with a conventional CMR exam (45–60 min). The compressed exam utilises 4D-flow together with a single breath-hold 3D-cine to provide a rapid, accurate quantitative assessment of the whole heart function. Outcome measures are (i) flow and chamber volume measurements and (ii) overall functional evaluation. Secondary analyses will explore clinical applications of 4D-flow-derived parameters, including wall shear stress, flow kinetic energy quantification, and vortex analysis in large-scale cohorts. A target of 1200 participants will enter the study across three sites. The analysis will be performed at a single core laboratory site. Pilot Results: We present a pilot analysis of 196 participants comparing flow measurements obtained by 4D-flow and conventional 2D phase contrast, which demonstrated moderate–good consistency in ascending aorta and main pulmonary artery flow measurements between the two techniques. Four-dimensional flow underestimated the flow compared with 2D-PC, by approximately 3 mL/beat in both vessels. Conclusions: We present the study protocol of a prospective non-inferiority study of a rapid cardiac MRI exam compared with conventional CMR. The pilot analysis supports the continuation of the study. Study Registration: This study is registered with the Australia and New Zealand Clinical Trials Registry (Registry number ACTRN12622000047796, Universal Trial Number: U1111-1270-6509, registered 17 January 2022—Retrospectively registered). Full article
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Figure 1
<p>The 4DCarE study flow chart and summary of imaging protocols. CMR: cardiac magnetic resonance; CMR<sub>FAST</sub>: rapid CMR protocol; CMR<sub>STD</sub>: conventional CMR protocol; DGE: delayed gadolinium enhancement; MRA: magnetic resonance angiography; SB: single breath; SAX: short-axis stack.</p>
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<p>The presence of implanted aortic valve (<b>left</b>) resulted in a flow pattern artefact in the ascending aorta (<b>right</b>). Color heatmap corresponds with flow velocity (red indicates high flow regions, green indicates low flow regions, blue indicates background static tissue). The cross (+) indicates the centre of regional of interest and the perpendicular lines are used to orientate the regional of interest.</p>
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<p>Flow measurements from nine poor-quality 4D-flow series showing discordant flows between the ascending aorta (AscAo) and main pulmonary artery (MPA).</p>
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<p>Correlation and Bland–Altman plots comparing measurements in the ascending aorta (AscAo) (top) and main pulmonary artery (MPA) between 2D-PC and 4D-flow performed by a CMR expert on a pilot cohort of 196 cases. RPC: reproducibility coefficient; SD: standard deviation.</p>
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<p>Correlation and Bland–Altman plots showing 2D-PC measurements in the ascending aorta (AscAo) (top) and main pulmonary artery (MPA), comparing a CMR expert with a trained annotator. RPC: reproducibility coefficient; SD: standard deviation.</p>
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<p>Correlation and Bland–Altman plots showing 4D-flow measurements in the ascending aorta (AscAo) (top) and main pulmonary artery (MPA), comparing a CMR expert with a trained annotator. RPC: reproducibility coefficient; SD: standard deviation.</p>
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<p>The top row (and magnified views): vessel boundary definition in 2D-PC contouring. (<b>a</b>) Initial contouring approach (red contour); (<b>b</b>) adjustment of windowing revealing pixels adjacent to the vessel wall excluded from the contour (black arrow); (<b>c</b>) a revised approach with expanded contour [<a href="#B24-diagnostics-14-02590" class="html-bibr">24</a>] (green contour) capturing all flow signal-containing pixels. The bottom row: Bland–Altman plots showing inter-observer reproducibility between two CMR experts using an unstandardised contouring approach (left) and a standardised expanded contouring approach (right), showing improved reproducibility following standardisation. RPC: reproducibility coefficient; SD: standard deviation.</p>
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<p>Impact of analysis location on the 4D-flow measurement of flow in AscAo: (<b>a</b>–<b>d</b>) four analysis locations (positions a–d from proximal to distal relative to the aortic valve, 2 cm apart as outlined on the velocity magnitude colour map. Net flow measured in L/min. Color heatmap corresponds with flow velocity (red indicates high flow regions, green indicates low flow regions, blue indicates background static tissue). The cross (+) indicates the centre of regional of interest and the perpendicular lines are used to orientate the regional of interest.</p>
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<p>CMR expert-measured flows at locations a–d along the ascending aorta, with flow curves showing median (solid lines) and one standard deviation (dotted lines) values for 20 participants. Repeated measures ANOVA was performed on the full cardiac cycle (<span class="html-italic">p</span> = 0.59), systolic phase (<span class="html-italic">p</span> = 0.40) and diastolic phase (<span class="html-italic">p</span> = 0.17). The measurements at the four locations are very similar as illustrated by the lines overlapping one another.</p>
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11 pages, 2478 KiB  
Article
Automated Quantification of Simple and Complex Aortic Flow Using 2D Phase Contrast MRI
by Rui Li, Hosamadin S. Assadi, Xiaodan Zhao, Gareth Matthews, Zia Mehmood, Ciaran Grafton-Clarke, Vaishali Limbachia, Rimma Hall, Bahman Kasmai, Marina Hughes, Kurian Thampi, David Hewson, Marianna Stamatelatou, Peter P. Swoboda, Andrew J. Swift, Samer Alabed, Sunil Nair, Hilmar Spohr, John Curtin, Yashoda Gurung-Koney, Rob J. van der Geest, Vassilios S. Vassiliou, Liang Zhong and Pankaj Gargadd Show full author list remove Hide full author list
Medicina 2024, 60(10), 1618; https://doi.org/10.3390/medicina60101618 - 3 Oct 2024
Viewed by 1369
Abstract
(1) Background and Objectives: Flow assessment using cardiovascular magnetic resonance (CMR) provides important implications in determining physiologic parameters and clinically important markers. However, post-processing of CMR images remains labor- and time-intensive. This study aims to assess the validity and repeatability of fully [...] Read more.
(1) Background and Objectives: Flow assessment using cardiovascular magnetic resonance (CMR) provides important implications in determining physiologic parameters and clinically important markers. However, post-processing of CMR images remains labor- and time-intensive. This study aims to assess the validity and repeatability of fully automated segmentation of phase contrast velocity-encoded aortic root plane. (2) Materials and Methods: Aortic root images from 125 patients are segmented by artificial intelligence (AI), developed using convolutional neural networks and trained with a multicentre cohort of 160 subjects. Derived simple flow indices (forward and backward flow, systolic flow and velocity) and complex indices (aortic maximum area, systolic flow reversal ratio, flow displacement, and its angle change) were compared with those derived from manual contours. (3) Results: AI-derived simple flow indices yielded excellent repeatability compared to human segmentation (p < 0.001), with an insignificant level of bias. Complex flow indices feature good to excellent repeatability (p < 0.001), with insignificant levels of bias except flow displacement angle change and systolic retrograde flow yielding significant levels of bias (p < 0.001 and p < 0.05, respectively). (4) Conclusions: Automated flow quantification using aortic root images is comparable to human segmentation and has good to excellent repeatability. However, flow helicity and systolic retrograde flow are associated with a significant level of bias. Overall, all parameters show clinical repeatability. Full article
(This article belongs to the Section Cardiology)
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<p>Illustration of aortic flow indices calculations. (<b>a</b>) Automated segmentation of phase contrast aortic root for the whole cardiac cycle. The red rectangle-outlined frame presents where the maximum aortic area is detected; (<b>b</b>) Aortic flow curve with illustrations of peak systole, late systole, systole, and diastole phases; (<b>c</b>) Flow displacement assessment; (<b>d</b>) Flow displacement rotational angle assessment. The gray areas denoted flow displacement ≤ 12% and were excluded in the calculations of rotational angle and rotational speed; (<b>e</b>) Flow reversal ratio assessment. The unit of the x-axis in each figure is the frame number.</p>
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<p>Bland–Altman plots for recorded flow indices.</p>
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26 pages, 7912 KiB  
Article
Investigation of Sonication Parameters for Large-Volume Focused Ultrasound-Mediated Blood–Brain Barrier Permeability Enhancement Using a Clinical-Prototype Hemispherical Phased Array
by Dallan McMahon, Ryan M. Jones, Rohan Ramdoyal, Joey Ying Xuan Zhuang, Dallas Leavitt and Kullervo Hynynen
Pharmaceutics 2024, 16(10), 1289; https://doi.org/10.3390/pharmaceutics16101289 - 30 Sep 2024
Viewed by 1281
Abstract
Background/Objectives: Focused ultrasound (FUS) and microbubble (MB) exposure is a promising technique for targeted drug delivery to the brain; however, refinement of protocols suitable for large-volume treatments in a clinical setting remains underexplored. Methods: Here, the impacts of various sonication parameters on blood–brain [...] Read more.
Background/Objectives: Focused ultrasound (FUS) and microbubble (MB) exposure is a promising technique for targeted drug delivery to the brain; however, refinement of protocols suitable for large-volume treatments in a clinical setting remains underexplored. Methods: Here, the impacts of various sonication parameters on blood–brain barrier (BBB) permeability enhancement and tissue damage were explored in rabbits using a clinical-prototype hemispherical phased array developed in-house, with real-time 3D MB cavitation imaging for exposure calibration. Initial experiments revealed that continuous manual agitation of MBs during infusion resulted in greater gadolinium (Gd) extravasation compared to gravity drip infusion. Subsequent experiments used low-dose MB infusion with continuous agitation and a low burst repetition frequency (0.2 Hz) to mimic conditions amenable to long-duration clinical treatments. Results: Key sonication parameters—target level (proportional to peak negative pressure), number of bursts, and burst length—significantly affected BBB permeability enhancement, with all parameters displaying a positive relationship with relative Gd contrast enhancement (p < 0.01). Even at high levels of BBB permeability enhancement, tissue damage was minimal, with low occurrences of hypointensities on T2*-weighted MRI. When accounting for relative Gd contrast enhancement, burst length had a significant impact on red blood cell extravasation detected in histological sections, with 1 ms bursts producing significantly greater levels compared to 10 ms bursts (p = 0.03), potentially due to the higher pressure levels required to generate equal levels of BBB permeability enhancement. Additionally, albumin and IgG extravasation correlated strongly with relative Gd contrast enhancement across sonication parameters, suggesting that protein extravasation can be predicted from non-invasive imaging. Conclusions: These findings contribute to the development of safer and more effective clinical protocols for FUS + MB exposure, potentially improving the efficacy of the approach. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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<p>Clinical-prototype FUS array system and PCI-based cavitation feedback control example. (<b>a</b>) Experimental setup. Animals were positioned supine with scalps coupled directly to degassed/deionized water within the FUS array. Ultraharmonic receivers were used for PCI-based control and subharmonic receivers were used for ICD. (<b>b</b>) Transmit/receive module. Each module contains 64 transducer elements (8 × 8 grid, 2.5 mm inter-element spacing, 60 transmit and 4 receive elements). (<b>c</b>) Transmit and receive array layouts. (<b>d</b>) PCI-based cavitation feedback control example from in vivo data. PNP was iteratively increased until the detection of coherent MB activity via PCI. On the burst prior to detection (t = 105 s, magenta; PNP = 0.49 MPa) there was no evidence of coherent MB activity on PCI and the SPTA intensity remained below the maximum levels observed during baseline pressure ramps without MBs in circulation (blue dotted line). Spatially coherent MB activity observed in PCI MIPs (t = 110 s, red; calibration PNP = 0.51 MPa) was accompanied by a large spike in the SPTA intensity. The driving voltage was reduced to the minimum system output until the calibration phase was completed at all targets. In this example, a target level of 50% was set (Tx phase PNP = 0.25 MPa for 60 bursts). There was no evidence of MB activity on PCI throughout the Tx phase during which the SPTA intensity remained below the maximum levels observed during baseline pressure ramps, as seen at t = 250 s (green). White scale bar = 4 mm. FUS: focused ultrasound; ICD: inertial cavitation detection; MB: microbubble; PCI: passive cavitation imaging; PNP: peak negative pressure; SPTA: spatial peak temporal average; Tx: treatment.</p>
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<p>Calibration phase cavitation feedback control scheme example. (<b>a</b>) An in vivo example of the cavitation feedback control scheme used during the calibration phase of FUS + MB exposures. PNP was increased each burst until satisfying PCI detection thresholds and/or exceeding the threshold for ICD ratio (<b>top panel</b>). In this example, PCI detection thresholds were satisfied on the 24th burst of the calibration phase (time = 115 s, green marker), corresponding to a divergence in PCI SPTA intensity versus the baseline pressure ramp (i.e., no MBs in circulation; <b>middle panel</b>). The ICD threshold was exceeded during the same burst (<b>bottom panel)</b>. (<b>b</b>) Frequency spectrum of filtered (8th order digital Butterworth filter, 380–400 kHz bandpass) RF data delay-and-summed to the voxel of maximum PCI SPTA intensity (green marker) for the calibration pressure burst (t = 115 s, blue line; PNP = 0.51 MPa), as well as that of the same voxel and sonicating PNP during a baseline pressure ramp without MBs in circulation (t = 115 s, red line; PNP = 0.51 MPa). The filtered delay-and-summed frequency spectrum for the burst prior to the calibration pressure with MBs in circulation is also shown (t = 110 s, light blue line; PNP = 0.49 MPa). (<b>c</b>) The mean unfiltered frequency spectrum across 4 subharmonic receivers used for ICD is shown for the calibration pressure burst (t = 115 s; blue line; PNP = 0.51 MPa), the same sonicating PNP during a baseline pressure ramp without MBs in circulation (t = 115 s; red line; PNP = 0.51 MPa), and the burst prior to the calibration pressure with MBs in circulation (t = 110 s; light blue line; PNP = 0.49). Light green rectangles indicate the bandwidth used for ICD calculations. White scale bar = 4 mm.</p>
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<p>Preliminary comparison of MB infusion methods. In a subset of rabbits (n = 4; aka Cohort #1), the impact of MB infusion method on BBB permeability enhancement was evaluated. (<b>a</b>–<b>d</b>) Target layout and sonication parameters are displayed in relation to T2w targeting scans for gravity drip (n = 24 targets) and continuous manual agitation (n = 32 targets) infusion methods. (<b>e</b>–<b>h</b>) T1w MRI highlights differences in relative Gd contrast enhancement between infusion methods and various sonication parameters. (<b>i</b>–<b>l</b>) No evidence of hypointensities in T2*w MRI were observed. (<b>m</b>) Relative Gd contrast enhancement is plotted for gravity drip and continuous manual agitation infusion; for each infusion method, only targets for which target level ≥ 70% and Tx phase bursts = 120, were considered (n = 8 targets for continuous manual infusion; n = 18 targets for gravity drip infusion). A significant difference was detected between infusion methods (<span class="html-italic">p</span> &lt; 0.01). White scale bars = 1 cm. A: anterior; L: left; P: posterior; R: right.</p>
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<p>Relative Gd contrast enhancement across sonication parameters. T1w MRI was performed approximately 10 min following the end of sonication. (<b>a</b>) Target-wise (n = 237) relative Gd contrast enhancement is plotted for each set of sonication parameters investigated. Burst length (<span class="html-italic">p</span> &lt; 0.01), target level (<span class="html-italic">p</span> &lt; 0.01), and number of Tx phase bursts (<span class="html-italic">p</span> &lt; 0.01) had significant effects on relative Gd contrast enhancement. Targets sonicated with 75% target level exhibited significantly greater levels of relative Gd contrast enhancement vs. 50% target level (<span class="html-italic">p</span> &lt; 0.01). At 75% target level, burst length had a significant impact on relative Gd contrast enhancement (<span class="html-italic">p</span> &lt; 0.01), with a significant difference between 1 ms vs. 10 ms burst lengths (<span class="html-italic">p</span> = 0.048). Number of Tx phase bursts also had a significant effect on relative Gd contrast enhancement at 75% target level (<span class="html-italic">p</span> &lt; 0.01). TL = target level. Representative examples of the targeting scheme (<b>b</b>,<b>e</b>), Gd contrast enhancement in T1w MRI (<b>c</b>,<b>f</b>), and T2*w MRI (<b>d</b>,<b>g</b>) are shown for sonications performed with 5 ms bursts and either 75% (<b>b</b>–<b>d</b>) or 50% (<b>e</b>–<b>g</b>) target levels. Number of Tx phase bursts range from 0 to 240 within each animal. White scale bars = 1 cm. A: anterior; L: left; P: posterior; R: right.</p>
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<p>RBC extravasation area across sonication parameters. In a subset of rabbits, the area of RBC extravasation was quantified in H&amp;E-stained tissue sections (66 targets, 5 rabbits). The animals were perfused 1.5 h following the start of FUS + MB exposure. (<b>a</b>) A significant correlation between relative Gd contrast enhancement and RBC area was observed across all sonication parameters (r<sup>2</sup> = 0.24, <span class="html-italic">p</span> &lt; 0.01). For targets sonicated with 5 ms bursts a significant correlation was also observed (r<sup>2</sup> = 0.33, <span class="html-italic">p</span> &lt; 0.01). At 75% target level, when relative Gd contrast enhancement was considered as a covariate, burst length (<span class="html-italic">p</span> &lt; 0.01) had significant effects on RBC extravasation. Post-hoc Tukey’s HSD test revealed a significant difference between 1 ms and 10 ms burst lengths (<span class="html-italic">p</span> = 0.03). (<b>b</b>) The target displaying the largest area of RBC extravasation observed (yellow border) was sonicated with 1 ms bursts, 75% target level, and 120 Tx phase bursts. This target displayed hypointense signal intensity on T2*w imaging (<a href="#pharmaceutics-16-01289-f0A3" class="html-fig">Figure A3</a>). The data point corresponding to this target is circled (yellow) in panel (<b>a</b>). (<b>c</b>) A histological image representative of 5 or 10 ms burst lengths and 75% target level is displayed (cyan border). Low levels of RBC extravasation are observed across the sonicated volume. The data point corresponding to this target is circled (cyan) in panel (<b>a</b>).</p>
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<p>Albumin and IgG immunofluorescence following sonication. In a subset of animals, immunofluorescent staining for albumin and IgG was performed on tissue sections from rabbits perfused for 1.5 h following the end of FUS + MB exposure (5 rabbits, 66 targets). A strong linear correlation was observed between relative Gd contrast enhancement and relative immunofluorescent signal intensity for both (<b>a</b>) albumin–GFP (r<sup>2</sup> = 0.63, <span class="html-italic">p</span> &lt; 0.01) and (<b>b</b>) IgG-DsRed (r<sup>2</sup> = 0.46, <span class="html-italic">p</span> &lt; 0.01). Across all sonication parameters, the target level had a significant effect on relative immunofluorescent signal intensity for both (<b>a</b>) albumin–GFP (<span class="html-italic">p</span> &lt; 0.01) and (<b>b</b>) IgG-DsRed (<span class="html-italic">p</span> &lt; 0.01). (<b>a</b>,<b>b</b>) When relative Gd contrast enhancement was considered as a covariate, no significant effect of target level or number of Tx phase bursts on relative immunofluorescent signal intensity of either protein were observed. (<b>c</b>) A representative example of albumin–GFP immunofluorescence for 8 posterior targets sonicated with 1 ms burst lengths and 75% target level is displayed. Areas of relatively homogeneous signal intensity across the target volume (cyan border) is contrasted with a more heterogeneous signal intensity (yellow border). Evidence of perivascular transport of albumin–GFP is shown in an area distant from any targeted volume (magenta border); IgG-DsRed signal intensity is not higher than background levels in this ROI.</p>
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<p>Comparison of estimated plasma concentration of Definity<sup>TM</sup> MBs over time. One compartment model of MB concentration in circulation over time for bolus (4 μL/kg) and infusion (0.8 μL/kg/min and 1.6 μL/kg/min) administration. Half-life of Definity<sup>TM</sup> was assumed to be 79 s [<a href="#B57-pharmaceutics-16-01289" class="html-bibr">57</a>]. For bolus administration, t = 0 represents the peak concentration in circulation. For infusion administration, t = 0 represents the start of delivery. Sonication durations are set to 120 s.</p>
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<p>Relative Gd contrast enhancement analysis. (<b>a</b>) An example of contrast enhanced T1w MRI collected following FUS + MB exposure. (<b>b</b>) ROIs selected for quantification of T1w signal intensity at targets (#1–16), as well as regions used as non-sonicated control tissue (C1–C4). Mean signal intensity within each targeted ROI was divided by mean signal intensity across the non-sonicated control ROIs to obtain relative Gd contrast enhancement values. White scale bars = 1 cm. A: anterior; L: left; P: posterior; R: right.</p>
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<p>T2*w hypointensity induced by FUS + MB exposure. (<b>a</b>,<b>b</b>) Sequential coronal slices from contrast enhanced T1w MRI collected following FUS + MB exposure. White arrows highlight a single target of increased BBB permeability. (<b>c</b>,<b>d</b>) Red arrows highlight a small area of hypointensity in T2*w MRI corresponding to the same target highlighted above. This target displayed the largest area of RBC extravasation in H&amp;E sections across all targets processed for histology. White scale bars = 1 cm. D: dorsal; L: left; R: right; V: ventral.</p>
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<p>Correlations between RBC extravasation area and relative Gd contrast enhancement for different numbers of Tx phase bursts. In a subset of rabbits, area of RBC extravasation was quantified in H&amp;E stained tissue sections (66 targets, 5 rabbits). Animals were perfused 1.5 h following the end of FUS + MB exposure. A significant correlation between relative Gd contrast enhancement and RBC area was observed across all sonication parameters (r<sup>2</sup> = 0.24, <span class="html-italic">p</span> &lt; 0.01). For targets sonicated with 60, 120, and 240 Tx phase bursts, significant correlations were also observed (60 Tx phase bursts: r<sup>2</sup> = 0.49, <span class="html-italic">p</span> &lt; 0.01; 120 Tx phase bursts: r<sup>2</sup> = 0.51, <span class="html-italic">p</span> &lt; 0.01; 240 Tx phase bursts: r<sup>2</sup> = 0.3, <span class="html-italic">p</span> = 0.03). For targets sonicated with 75% target level, when relative Gd contrast enhancement was considered as a covariate, number of Tx phase bursts (<span class="html-italic">p</span> &lt; 0.01) and burst length (<span class="html-italic">p</span> &lt; 0.01; <a href="#pharmaceutics-16-01289-f005" class="html-fig">Figure 5</a>a) had significant effects on RBC extravasation. Post-hoc analysis revealed no significant differences between any paired comparison of Tx phase burst numbers.</p>
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<p>Correlations between protein immunofluorescence and relative Gd contrast enhancement for different numbers of Tx phase bursts. In a subset of animals, immunofluorescent staining for albumin and IgG was performed on tissue sections from rabbits perfused 1.5 h following the end of FUS + MB exposure (5 rabbits, 66 targets). A strong linear correlation was observed between relative Gd contrast enhancement and relative immunofluorescent signal intensity for both (<b>a</b>) albumin-GFP (r<sup>2</sup> = 0.63, <span class="html-italic">p</span> &lt; 0.01) and (<b>b</b>) IgG-DsRed (r<sup>2</sup> = 0.46, <span class="html-italic">p</span> &lt; 0.01). When targets sonicated with an equal number of Tx phase bursts were considered, significant correlations were observed for 60, 120, and 240 Tx phase bursts for both albumin-GFP (60 Tx phase bursts: r<sup>2</sup> = 0.57, <span class="html-italic">p</span> &lt; 0.01; 120 Tx phase bursts: r<sup>2</sup> = 0.79, <span class="html-italic">p</span> &lt; 0.01; 240 Tx phase bursts: r<sup>2</sup> = 0.73, <span class="html-italic">p</span> &lt; 0.01) and IgG-DsRed (60 Tx phase bursts: r<sup>2</sup> = 0.31, <span class="html-italic">p</span> = 0.05; 120 Tx phase bursts: r<sup>2</sup> = 0.76, <span class="html-italic">p</span> &lt; 0.01; 240 Tx phase bursts: r<sup>2</sup> = 0.60, <span class="html-italic">p</span> &lt; 0.01). (<b>a</b>,<b>b</b>) When relative Gd contrast enhancement was considered as a covariate, no significant effect of the number of Tx phase bursts on relative immunofluorescent signal intensity of either protein were observed.</p>
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21 pages, 2095 KiB  
Article
Brain Volumetric Analysis Using Artificial Intelligence Software in Premanifest Huntington’s Disease Individuals from a Colombian Caribbean Population
by Margarita R. Ríos-Anillo, Mostapha Ahmad, Johan E. Acosta-López, Martha L. Cervantes-Henríquez, Maria C. Henao-Castaño, Maria T. Morales-Moreno, Fabián Espitia-Almeida, José Vargas-Manotas, Cristian Sánchez-Barros, David A. Pineda and Manuel Sánchez-Rojas
Biomedicines 2024, 12(10), 2166; https://doi.org/10.3390/biomedicines12102166 - 24 Sep 2024
Viewed by 1154
Abstract
Background and objectives: The premanifest phase of Huntington’s disease (HD) is characterized by the absence of motor symptoms and exhibits structural changes in imaging that precede clinical manifestation. This study aimed to analyze volumetric changes identified through brain magnetic resonance imaging (MRI) processed [...] Read more.
Background and objectives: The premanifest phase of Huntington’s disease (HD) is characterized by the absence of motor symptoms and exhibits structural changes in imaging that precede clinical manifestation. This study aimed to analyze volumetric changes identified through brain magnetic resonance imaging (MRI) processed using artificial intelligence (AI) software in premanifest HD individuals, focusing on the relationship between CAG triplet expansion and structural biomarkers. Methods: The study included 36 individuals descending from families affected by HD in the Department of Atlántico. Sociodemographic data were collected, followed by peripheral blood sampling to extract genomic DNA for quantifying CAG trinucleotide repeats in the Huntingtin gene. Brain volumes were evaluated using AI software (Entelai/IMEXHS, v4.3.4) based on MRI volumetric images. Correlations between brain volumes and variables such as age, sex, and disease status were determined. All analyses were conducted using SPSS (v. IBM SPSS Statistics 26), with significance set at p < 0.05. Results: The analysis of brain volumes according to CAG repeat expansion shows that individuals with ≥40 repeats evidence significant increases in cerebrospinal fluid (CSF) volume and subcortical structures such as the amygdalae and left caudate nucleus, along with marked reductions in cerebral white matter, the cerebellum, brainstem, and left pallidum. In contrast, those with <40 repeats show minimal or moderate volumetric changes, primarily in white matter and CSF. Conclusions: These findings suggest that CAG expansion selectively impacts key brain regions, potentially influencing the progression of Huntington’s disease, and that AI in neuroimaging could identify structural biomarkers long before clinical symptoms appear. Full article
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Figure 1
<p>Comparison of global brain volumes according to CAG expansion. This figure compares the global brain volumes in three groups of individuals with different CAG triplet expansions: ≤26 (normal), 27 – 35 (intermediate), and &gt;40 (full penetrance). The structures evaluated include the brain parenchyma volume (<b>A</b>), cerebrospinal fluid (CSF) volume (<b>B</b>), gray matter volume (<b>C</b>), white matter volume (<b>D</b>). The <span class="html-italic">p</span> values indicate the statistical significance of the observed differences: (*** <span class="html-italic">p</span> &lt; 0.00001).</p>
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<p>Subcortical structure volumes according to CAG triplet expansion. This figure compares the volumes of various subcortical brain structures in three groups of individuals with different CAG triplet expansions: ≤26 (normal), 27–35 (intermediate), and &gt;40 (full penetrance). The structures evaluated include the amygdala (<b>A</b>,<b>F</b>), caudate (<b>B</b>,<b>G</b>), pallidum (<b>C</b>,<b>H</b>), putamen (<b>D</b>,<b>I</b>), and thalamus (<b>E</b>,<b>J</b>), in both the left and right hemispheres. The <span class="html-italic">p</span> values indicate the statistical significance of the observed differences: * (<span class="html-italic">p</span> &lt; 0.002), ** (<span class="html-italic">p</span> &lt; 0.0002), and **** (<span class="html-italic">p</span> &lt; 0.000001).</p>
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<p>Subcortical structure volumes according to CAG triplet expansion. This figure compares the volumes of various subcortical brain structures in three groups of individuals with different CAG triplet expansions: ≤26 (normal), 27–35 (intermediate), and &gt;40 (full penetrance). The structures evaluated include the amygdala (<b>A</b>,<b>F</b>), caudate (<b>B</b>,<b>G</b>), pallidum (<b>C</b>,<b>H</b>), putamen (<b>D</b>,<b>I</b>), and thalamus (<b>E</b>,<b>J</b>), in both the left and right hemispheres. The <span class="html-italic">p</span> values indicate the statistical significance of the observed differences: * (<span class="html-italic">p</span> &lt; 0.002), ** (<span class="html-italic">p</span> &lt; 0.0002), and **** (<span class="html-italic">p</span> &lt; 0.000001).</p>
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<p>Ventricular system volumes according to CAG triplet expansion. This figure compares the volumes in three groups of individuals with different CAG triplet expansions: ≤26 (normal), 27–35 (intermediate), and &gt;40 (full penetrance). The evaluated structures include the 4th ventricle (<b>A</b>) and supratentorial ventricle (<b>B</b>). The <span class="html-italic">p</span> values indicate the statistical significance of the observed differences: (*** <span class="html-italic">p</span> &lt; 0.00001, **** <span class="html-italic">p</span> &lt; 0.000001).</p>
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<p>Comparison of infratentorial structure volumes according to CAG triplet expansion. This figure compares the volumes of infratentorial structures in three groups of individuals with different CAG triplet expansions: ≤26 (normal), 27–35 (intermediate), and &gt;40 (full penetrance). The evaluated structures include the left cerebellar white matter volume (<b>A</b>), right cerebellar white matter (<b>B</b>), left cerebellar gray matter (<b>C</b>), right cerebellar, gray matter (<b>D</b>), and brainstem (<b>E</b>). The <span class="html-italic">p</span> values indicate the statistical significance of the observed differences: (* <span class="html-italic">p</span> &lt; 0.002), ** <span class="html-italic">p</span> &lt; 0.0002).</p>
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<p>Cortical and hippocampal volumes according to CAG triplet expansion. This figure compares the volumes of various cortical areas and the hippocampus in three groups of individuals with different CAG triplet expansions: ≤26 (normal), 27–35 (intermediate), and &gt;40 (full penetrance). The evaluated structures include the frontal cortex (<b>A</b>), insular cortex (<b>B</b>), occipital cortex (<b>C</b>), parietal cortex (<b>D</b>), temporal cortex (<b>E</b>), left hippocampus (<b>F</b>), and right hippocampus (<b>G</b>). The <span class="html-italic">p</span> values indicate the statistical significance of the observed differences: (<span class="html-italic">p</span> &gt; 0.05).</p>
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<p>Brain Volumetry via Nuclear Magnetic Resonance Imaging in Individuals with CAG Triplet Expansion.</p>
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19 pages, 4678 KiB  
Communication
Automated MRI Video Analysis for Pediatric Neuro-Oncology: An Experimental Approach
by Artur Fabijan, Agnieszka Zawadzka-Fabijan, Robert Fabijan, Krzysztof Zakrzewski, Emilia Nowosławska, Róża Kosińska and Bartosz Polis
Appl. Sci. 2024, 14(18), 8323; https://doi.org/10.3390/app14188323 - 15 Sep 2024
Cited by 1 | Viewed by 864
Abstract
Over the past year, there has been a significant rise in interest in the application of open-source artificial intelligence models (OSAIM) in the field of medicine. An increasing number of studies focus on evaluating the capabilities of these models in image analysis, including [...] Read more.
Over the past year, there has been a significant rise in interest in the application of open-source artificial intelligence models (OSAIM) in the field of medicine. An increasing number of studies focus on evaluating the capabilities of these models in image analysis, including magnetic resonance imaging (MRI). This study aimed to investigate whether two of the most popular open-source AI models, namely ChatGPT 4o and Gemini Pro, can analyze MRI video sequences with single-phase contrast in sagittal and frontal projections, depicting a posterior fossa tumor corresponding to a medulloblastoma in a child. The study utilized video files from single-phase contrast-enhanced head MRI in two planes (frontal and sagittal) of a child diagnosed with a posterior fossa tumor, type medulloblastoma, confirmed by histopathological examination. Each model was separately provided with the video file, first in the sagittal plane, analyzing three different sets of commands from the most general to the most specific. The same procedure was applied to the video file in the frontal plane. The Gemini Pro model did not conduct a detailed analysis of the pathological change but correctly identified the content of the video file, indicating it was a brain MRI, and suggested that a specialist in the field should perform the evaluation. Conversely, ChatGPT 4o conducted image analysis but failed to recognize that the content was MRI. The attempts to detect the lesion were random and varied depending on the plane. These models could not accurately identify the video content or indicate the area of the neoplastic change, even after applying detailed queries. The results suggest that despite their widespread use in various fields, these models require further improvements and specialized training to effectively support medical diagnostics. Full article
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<p>Progression of the questions in the study from general to specific with their specific reasoning.</p>
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<p>Sagittal plane MRI scan (<b>A</b>) and frontal plane MRI scan (<b>B</b>) show a multifocal cystic lesion with a solid component, mainly in the medial part, peripherally in the left cerebellar hemisphere. The lesion measures approximately 53 × 44 × 40 mm (SD × AP × CC) and adheres to the inner plate of the occipital bone, causing its thinning, and to the cerebellar tentorium. The solid part of the lesion shows fairly uniform contrast enhancement.</p>
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<p>Figure shows a fragment of the answer from Gemini Pro regarding the analyzed MRI video material.</p>
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<p>Analysis performed by ChatGPT 4o for the frontal plane. The results of the motion detection and contour analysis indicate the following: 1. Contours in Frames (<b>Left side</b>). The green contours highlight regions where significant changes or movements have occurred between consecutive frames. These regions could correspond to moving objects, changing light conditions, or other dynamic elements in the video. 2. Thresholded Difference (<b>Right side</b>): The binary images show the areas where the differences between frames exceed a certain threshold. White areas represent significant changes, while black areas indicate little to no change.</p>
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<p>Analysis performed by ChatGPT 4o for the sagittal plane. The frames with segmentation and annotations show the following: Segmentation: Green contours highlight potential areas of interest in the images. Annotation Detection: Red lines indicate detected line segments, which may correspond to annotations such as arrows.</p>
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<p>ChatGPT 4o’s response regarding tumor detection in the frontal plane. The analysis of the first frame indicates two potential tumor regions, which are highlighted with green contours.</p>
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<p>ChatGPT 4o’s response regarding tumor detection in the sagittal plane. Potential areas of interest in the three selected frames are highlighted. The red rectangles indicate regions where there might be abnormal enhancement, suggesting the presence of a tumor.</p>
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20 pages, 12662 KiB  
Review
Free-Running Cardiac and Respiratory Motion-Resolved Imaging: A Paradigm Shift for Managing Motion in Cardiac MRI?
by Robert J. Holtackers and Matthias Stuber
Diagnostics 2024, 14(17), 1946; https://doi.org/10.3390/diagnostics14171946 - 3 Sep 2024
Viewed by 1163
Abstract
Cardiac magnetic resonance imaging (MRI) is widely used for non-invasive assessment of cardiac morphology, function, and tissue characteristics due to its exquisite soft-tissue contrast. However, it remains time-consuming and requires proficiency, making it costly and limiting its widespread use. Traditional cardiac MRI is [...] Read more.
Cardiac magnetic resonance imaging (MRI) is widely used for non-invasive assessment of cardiac morphology, function, and tissue characteristics due to its exquisite soft-tissue contrast. However, it remains time-consuming and requires proficiency, making it costly and limiting its widespread use. Traditional cardiac MRI is inefficient as signal acquisition is often limited to specific cardiac phases and requires complex view planning, parameter adjustments, and management of both respiratory and cardiac motion. Recent efforts have aimed to make cardiac MRI more efficient and accessible. Among these innovations, the free-running framework enables 5D whole-heart imaging without the need for an electrocardiogram signal, respiratory breath-holding, or complex planning. It uses a fully self-gated approach to extract cardiac and respiratory signals directly from the acquired image data, allowing for more efficient coverage in time and space without the need for electrocardiogram gating, triggering, navigators, or breath-holds. This review provides a comprehensive overview of the free-running framework, detailing its history, concepts, recent improvements, and clinical applications. Full article
(This article belongs to the Special Issue New Trends and Advances in Cardiac Imaging)
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<p>One of the first MRI images of the heart was acquired in a volunteer using the Aberdeen NMR imager in 1979, before the spin-warp breakthrough. Although the contours of the body and some internal structures can be recognized, severe artefacts caused by cardiac motion were present preventing its clinical use. Image courtesy of Bill Edelstein.</p>
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<p>Panel (<b>A</b>) Schematic overview of 3D radial sampling using a spiral phyllotaxis readout pattern (also known as an interleave). When the pre-defined number of radial spokes of a single interleave has been acquired, the next interleave will start which is rotated about the golden angle (~137.5°) from the previous one. Panel (<b>B</b>) With an increasing number of interleaves, an increasingly dense 3D kooshball of data points is obtained. After a pre-defined number of interleaves, the free-running acquisition is finished.</p>
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<p>A schematic overview of enabling self-gating (SG) in 3D radial MRI by inserting a radial spoke in the superior-inferior direction at the start of each interleaf. Due to the continuous acquisition, an SG signal is obtained periodically as defined by the number of spokes per interleave (i.e., segments) and the repetition time (TR). With a TR of 3.5 ms and 20 segments per interleave (as shown), an SG signal is acquired every 70 ms and can be used to extract cardiac and respiratory motion information for total SG.</p>
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<p>Panel (<b>A</b>) By extracting all superior-inferior (SI) spokes from each consecutive interleave, a self-gating (SG) signal is obtained. Panel (<b>B</b>) Using principal component analysis and filtering of this SG signal, the main respiratory and cardiac frequencies can be derived, and the respiratory and cardiac signature curves can be extracted. Panel (<b>C</b>) Using the respiratory and cardiac motion signals, all acquired radial spokes can be retrospectively binned into a variable number of cardiac phases and respiratory motion states. Using a compressed-sensing reconstruction, a 3D volume is obtained for each bin, ultimately leading to a 5D cardiac and respiratory motion-resolved dataset.</p>
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<p>The obtained 5D image dataset can be visualised in various ways. (<b>A</b>) By fixing a specific respiratory motion state and looping through the cardiac phases, a cardiac 3D cine image is obtained (x-y-z-cardiac). (<b>B</b>) By fixing a specific cardiac phase and looping through the respiratory motion states, a respiratory 3D cine image is obtained (x-y-z-respiratory). (<b>C</b>) By fixing both a specific cardiac phase and respiratory motion state, a static 3D volume is obtained (x-y-z). For both dynamic 3D cines (<b>A</b>,<b>B</b>) and the static 3D volume (<b>C</b>), every desired (double) oblique cardiac view can be retrospectively selected using a multiplanar reconstruction.</p>
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<p>Panel (<b>A</b>) Diastolic and systolic coronary reformats of paediatric patients after ferumoxytol injection under general anaesthesia and intubation, and under sedation and free-breathing. Data were collected using the 5D free-running framework. The orange arrowheads indicate the right coronary artery (RCA), while the blue arrowheads indicate the left main (LM) and left anterior descending (LAD) coronary arteries. It can be observed that image quality and vessel conspicuity appear similar in the two indicated cardiac phases, as well as that image quality is comparable between intubated and free-breathing subjects. Panel (<b>B</b>) Coronary reformats for three intubated and one free-breathing paediatric subjects for simultaneous visualisation of the RCA ostium (orange arrowheads) and LM artery ostium (blue arrowheads). The arrowheads with a red glow highlight anomalous coronary vessel anatomy. Figure created using the original source images by Roy et al. [<a href="#B29-diagnostics-14-01946" class="html-bibr">29</a>] with author permission.</p>
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<p>Cardiac cine imaging in transversal, coronal, and sagittal views, and in left two-chamber, four-chamber, and short-axis views (using multiplanar reconstructions), acquired using the 5D free-running framework in a healthy adult subject using a 1-min and 6-min acquisition without contrast at 1.5 T. Although the significantly increased noise, lower image quality, and lower observer confidence for the 1-min acquisition are apparent, cardiac volumes and function were still comparable to reference standard 2D breath-hold cine imaging (not shown in this figure).</p>
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<p>Panel (<b>A</b>) Magnitude images and phase-difference images for all three velocity-encoding directions (V<sub>x</sub>, V<sub>y</sub>, and V<sub>z</sub>) in a transversal (TRA), coronal (COR), and sagittal (SAG) view for a specific time point during systole of a 41-year-old man with bicuspid aortic valve disease. Panel (<b>B</b>) Peak systolic velocity maximum intensity projections (MIPs) and streamlines show good agreement between conventional navigator-gated 4D flow and free-running 5D flow imaging, with some overestimation in the ascending aorta (AAo) and underestimation in the arch and descending aorta (DAo) as indicated by the white arrows. Panel (<b>C</b>) Flow curves at three locations in the aorta, as indicated by the red lines in panel (<b>B</b>), demonstrate good agreement between the two techniques. The underestimation in the arch and DAo for 5D flow can be observed. LV = left ventricle, SVC = superior vena cava. Figure created using the original source images by Ma et al. [<a href="#B52-diagnostics-14-01946" class="html-bibr">52</a>] with author permission.</p>
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<p>Panel (<b>A</b>) Water-only and fat-only images, and corresponding parametric maps of water fraction and fat fraction of a healthy adult subject as obtained using the proposed 6D free-running framework (x-y-z-cardiac-respiratory-echo) at 1.5 T. Panel (<b>B</b>) Cardiac fat fraction maps in a transversal view for each phase of the cardiac cycle during end-expiration as obtained using the proposed 6D free-running framework in a healthy adult subject at 1.5 T, allowing tracking of the displacement of pericardial fatty regions throughout the cardiac cycle. Figure created using the original source images by Mackowiak et al. [<a href="#B58-diagnostics-14-01946" class="html-bibr">58</a>] with author permission.</p>
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<p>Panel (<b>A</b>) Comparison of anatomical images acquired by the 5D free-running framework using a standard balanced steady-state free-precession (bSSFP) and fast-interrupted steady-state (FISS) acquisition at 3 T. The 5D datasets were multiplanar reformatted to a sagittal view, and images are shown in systole and diastole at both end-expiration and end-inspiration. The yellow lines help to indicate respiratory motion. The red arrows indicate the decrease in streaking artefacts in FISS compared to bSSFP. Panel (<b>B</b>) Comparison of coronary reformats obtained using both bSSFP and FISS, at both 1.5 T and 3 T. The water–fat cancellation artefacts at the coronary vessel borders can be observed in the bSSFP images, while these are absent in the FISS images. Panel (<b>C</b>) Comparison of anatomical images using a bSSFP and FISS acquisition at 1.5 T. Both 5D image data were binned into 16 cardiac phases and four respiratory motion states, of which eight cardiac phases in the end-expiratory motion state are shown in coronal view for each method. The red arrows indicate cardiac regions containing fat that is suppressed using FISS but not using bSSFP. Panel (<b>D</b>) Comparison of anatomical images using a bSSFP and FISS acquisition at 3 T. Both 5D image data were binned into 26 cardiac phases and four respiratory motion states, of which eight cardiac phases in the end-expiratory motion state are shown in coronal view for each method. The red arrows indicate cardiac regions containing fat that is suppressed using FISS but not using bSSFP. Figure created using the original source images by Bastiaansen et al. [<a href="#B69-diagnostics-14-01946" class="html-bibr">69</a>] with author permission.</p>
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<p>Cardiac cine imaging in various short-axis, and left two-chamber and four-chamber cardiac views (using multiplanar reconstructions), acquired using the 5D free-running framework in two healthy adult subjects using a 7 min acquisition without contrast at 0.55 T. Despite the significantly increased noise and decreased blood–myocardium contrast at low field compared to 1.5 T, cardiac anatomy and function can still be depicted in detail using the fully automated free-running framework without the need for an ECG signal or repetitive breath-holding.</p>
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21 pages, 1614 KiB  
Review
WFUMB Review Paper. Incidental Findings in Otherwise Healthy Subjects, How to Manage: Liver
by Roxana Șirli, Alina Popescu, Christian Jenssen, Kathleen Möller, Adrian Lim, Yi Dong, Ioan Sporea, Dieter Nürnberg, Marieke Petry and Christoph F. Dietrich
Cancers 2024, 16(16), 2908; https://doi.org/10.3390/cancers16162908 - 21 Aug 2024
Viewed by 841
Abstract
An incidental focal liver lesion (IFLL) is defined as a hepatic lesion identified in a patient imaged for an unrelated reason. They are frequently encountered in daily practice, sometimes leading to unnecessary, invasive and potentially harmful follow-up investigations. The clinical presentation and the [...] Read more.
An incidental focal liver lesion (IFLL) is defined as a hepatic lesion identified in a patient imaged for an unrelated reason. They are frequently encountered in daily practice, sometimes leading to unnecessary, invasive and potentially harmful follow-up investigations. The clinical presentation and the imaging aspects play an important role in deciding if, and what further evaluation, is needed. In low-risk patients (i.e., without a history of malignant or chronic liver disease or related symptoms), especially in those younger than 40 years old, more than 95% of IFLLs are likely benign. Shear Wave liver Elastography (SWE) of the surrounding liver parenchyma should be considered to exclude liver cirrhosis and for further risk stratification. If an IFLL in a low-risk patient has a typical appearance on B-mode ultrasound of a benign lesion (e.g., simple cyst, calcification, focal fatty change, typical hemangioma), no further imaging is needed. Contrast-Enhanced Ultrasound (CEUS) should be considered as the first-line contrast imaging modality to differentiate benign from malignant IFLLs, since it has a similar accuracy to contrast-enhanced (CE)-MRI. On CEUS, hypoenhancement of a lesion in the late vascular phase is characteristic for malignancy. CE-CT should be avoided for characterizing probable benign FLL and reserved for staging once a lesion is proven malignant. In high-risk patients (i.e., with chronic liver disease or an oncological history), each IFLL should initially be considered as potentially malignant, and every effort should be made to confirm or exclude malignancy. US-guided biopsy should be considered in those with unresectable malignant lesions, particularly if the diagnosis remains unclear, or when a specific tissue diagnosis is needed. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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<p>A 35-year-old male presents for consultation for nausea and diarrhea with acute onset. Ultrasound revealed a large, anechoic lesion (between markers x and +) with thin, irregular walls, situated in segment 4–5—typical aspect of simple biliary cyst.</p>
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<p>A 40-year-old female presents for consultation for right renal colic. Ultrasound revealed 2 cystic lesions (between markers x, and &lt;) with thick walls and septa, situated in the right liver lobe. Anti Echinococcus granulosis antibodies positive. Typical aspect of hydatid cyst.</p>
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<p>A 43 year-old obese female (BMI 32 kg/m<sup>2</sup>) presents for consultation for routine US examination. Ultrasound revealed a large hypoechoic area in segments VII, VIII with clear linear delineation from the rest of the liver. Just anterior to the portal vein (PV) another hypoechoic clearly delineated lesion (between markers +). Liver function tests normal, elevated triglycerides and glycemia, normal values of liver stiffness by 2D-SWE elastography. Typical aspect of focal fatty sparing.</p>
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<p>A 32-year-old male presents for consultation for occasional epigastric pain. Ultrasound revealed a hyperechoic, homogeneous, well delineated lesion (between markers +) 23 mm in diameter, situated in segment V—aspect of typical hemangioma.</p>
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<p>Several echogenic FLL with a hypoechoic peripheral rim “halo sign” (between arrows)—typical for metastases, in a 68-year-old patient with a history of colonic cancer.</p>
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20 pages, 4364 KiB  
Article
3D Quantitative-Amplified Magnetic Resonance Imaging (3D q-aMRI)
by Itamar Terem, Kyan Younes, Nan Wang, Paul Condron, Javid Abderezaei, Haribalan Kumar, Hillary Vossler, Eryn Kwon, Mehmet Kurt, Elizabeth Mormino, Samantha Holdsworth and Kawin Setsompop
Bioengineering 2024, 11(8), 851; https://doi.org/10.3390/bioengineering11080851 - 20 Aug 2024
Cited by 1 | Viewed by 1608
Abstract
Amplified MRI (aMRI) is a promising new technique that can visualize pulsatile brain tissue motion by amplifying sub-voxel motion in cine MRI data, but it lacks the ability to quantify the sub-voxel motion field in physical units. Here, we introduce a novel post-processing [...] Read more.
Amplified MRI (aMRI) is a promising new technique that can visualize pulsatile brain tissue motion by amplifying sub-voxel motion in cine MRI data, but it lacks the ability to quantify the sub-voxel motion field in physical units. Here, we introduce a novel post-processing algorithm called 3D quantitative amplified MRI (3D q-aMRI). This algorithm enables the visualization and quantification of pulsatile brain motion. 3D q-aMRI was validated and optimized on a 3D digital phantom and was applied in vivo on healthy volunteers for its ability to accurately measure brain parenchyma and CSF voxel displacement. Simulation results show that 3D q-aMRI can accurately quantify sub-voxel motions in the order of 0.01 of a voxel size. The algorithm hyperparameters were optimized and tested on in vivo data. The repeatability and reproducibility of 3D q-aMRI were shown on six healthy volunteers. The voxel displacement field extracted by 3D q-aMRI is highly correlated with the displacement measurements estimated by phase contrast (PC) MRI. In addition, the voxel displacement profile through the cerebral aqueduct resembled the CSF flow profile reported in previous literature. Differences in brain motion was observed in patients with dementia compared with age-matched healthy controls. In summary, 3D q-aMRI is a promising new technique that can both visualize and quantify pulsatile brain motion. Its ability to accurately quantify sub-voxel motion in physical units holds potential for the assessment of pulsatile brain motion as well as the indirect assessment of CSF homeostasis. While further research is warranted, 3D q-aMRI may provide important diagnostic information for neurological disorders such as Alzheimer’s disease. Full article
(This article belongs to the Special Issue Novel MRI Techniques and Biomedical Image Processing)
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<p>The 3D q-aMRI algorithm pipeline begins with the decomposition of volumetric cine MRI using the 3D complex steerable pyramid. This process separates the images into various scales and orientations, isolating different spatial frequency components. The decomposed images are then split into amplitude and phase components, with the phases encoding information about sub-voxel motion. Next, the phase components are temporally filtered at each spatial location, orientation, and scale to enhance significant temporal changes. These filtered phases are split and proceed along two paths: the original amplification path for visualization and the quantification path for generating voxel displacement maps. For quantitative estimation, the data undergo the estimation of the spatial phase derivative. This involves estimating the spatial phase derivative from the decomposed image. The voxel displacement field is then calculated by solving a least squares optimization objective. This formula calculates the best-fit voxel displacement field that aligns the phase derivatives with the phase temporal changes. The color-coded images display the estimated voxel displacements in the axial (L/R direction, white arrow), sagittal (S/I direction, white arrow), and coronal (S/I direction, white arrow) planes. The plus sign indicates the positive direction of motion.</p>
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<p>Validation of 3D q-aMRI on a 3D cylinder phantom (initial height <math display="inline"><semantics> <msub> <mi>h</mi> <mn>0</mn> </msub> </semantics></math> and <math display="inline"><semantics> <msub> <mi>r</mi> <mn>0</mn> </msub> </semantics></math> radius) that undergoes cyclic tension and compression. (<b>a</b>) The phantom at reference time <math display="inline"><semantics> <msub> <mi>t</mi> <mn>0</mn> </msub> </semantics></math> and deformation time <math display="inline"><semantics> <msub> <mi>t</mi> <mi>i</mi> </msub> </semantics></math>. (<b>b</b>) Error as a function of displacement in the absence of noise.</p>
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<p><span class="html-italic">In vivo</span> validation of the 3D q-aMRI against the observed signal in 3D aMRI. The 4D cine data are amplified by 3D aMRI. In addition, the first volume in the cine data is warped by an amplified version of the estimated motion field, and normalized temporal variance maps are calculated for both amplified movies. The maps suggest that 3D q-aMRI quantification output matches the motion observed qualitatively in 3D aMRI.</p>
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<p>Normalized temporal standard deviation maps of the amplified videos for different pyramid levels. The data were amplified with an amplification parameter of 30 with a Gaussian window with <math display="inline"><semantics> <mrow> <mi>σ</mi> <mo>=</mo> <mn>5</mn> </mrow> </semantics></math>. Coherent motion exists mainly in the first two levels of the steerable pyramid.</p>
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<p>Normalized temporal standard deviation maps of the amplified videos for different temporal frequency bands. The data were amplified with an amplification parameter of 30 with a Gaussian window with <math display="inline"><semantics> <mrow> <mi>σ</mi> <mo>=</mo> <mn>5</mn> </mrow> </semantics></math>. Motion was extracted using the first two levels of the steerable pyramid. Coherent motion exists mainly in the one to four heart rate harmonics band.</p>
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<p>The pulsatile brain motion in the sagittal (S/I direction, indicated by a white arrow) and axial (L/R direction, indicated by a white arrow) for different standard deviation sizes of the Gaussian window. The Gaussian smoothing reduces the noise level in the estimated motion field. For standard deviations larger than <math display="inline"><semantics> <mrow> <mi>σ</mi> <mo>=</mo> <mn>5</mn> </mrow> </semantics></math>, the estimated motion field is smooth and generally remains constant.</p>
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<p>The pulsatile brain motion in the sagittal (S/I direction, indicated by a white arrow) and axial (L/R direction, indicated by a white arrow) directions for different isotropic spatial resolutions. Plus sign represent the positive direction of motion. As can be seen, the algorithm can robustly estimate the motion field for different image resolutions (up to 1.8 mm isotropic voxel size). Note that the dark blue/red regions (red arrows) in the sagittal plane point to the basilar artery, which exhibits apparent motion (larger than 1.5 pixels).</p>
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<p>(<b>a</b>) Comparison between PC-MRI (top) and 3D q-aMRI (bottom) for sagittal (S/I direction), coronal (S/I direction), and axial (L/R direction) planes. The estimated field captures the relative brain tissue deformation over time and the physical change in shape of the ventricles by the relative movement of the surrounding tissues. (<b>b</b>) The extracted flow/motion profile through the cerebral aqueduct as extracted by 3D q-aMRI (left), which is comparable to that reported by [<a href="#B46-bioengineering-11-00851" class="html-bibr">46</a>] as shown in the inset (right). Note that [<a href="#B46-bioengineering-11-00851" class="html-bibr">46</a>] the graph seen here is normalized, but the actual CSF flow values reported were an order of magnitude higher than the 3D q-aMRI flow profile.</p>
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<p>(<b>a</b>) The average (over different brain regions) voxel displacement profile for two subjects (<math display="inline"><semantics> <msub> <mi>S</mi> <mn>1</mn> </msub> </semantics></math> and <math display="inline"><semantics> <msub> <mi>S</mi> <mn>3</mn> </msub> </semantics></math>) in the S/I direction for eight scans (<math display="inline"><semantics> <msub> <mi>t</mi> <mn>0</mn> </msub> </semantics></math> to <math display="inline"><semantics> <msub> <mi>t</mi> <mn>7</mn> </msub> </semantics></math>). Top—the brain regions (lateral ventricles, 3rd ventricle, 4th ventricle, brainstem, and cerebellum) where the average voxel displacement was estimated. Bottom—the first two columns depict the voxel displacement profile for all scans, for each of the two subjects. The black line represents the average motion over all scans, together with an error bar (95% confidence interval). The last column depicts the average motion for all six subjects, along with error bars representing the 95% confidence interval. The results indicate high repeatability across the time points within each subject, with similar motion patterns but different magnitudes across all subjects. (<b>b</b>) The boxplots for each brain region and the Intraclass Correlation Coefficient (ICC) of the dynamic time warping (DTW) distance. The plus sign denotes an outlier.</p>
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<p>Depicts diffuse reduction in brain bulk displacement on both the sagittal (S/I direction, white arrow) and axial (L/R direction, white arrow) planes for elderly adults with MCI due to dementia (70-year-old female) compared to an elderly control (74-year-old female) plus sign represent the positive direction of motion. In addition, loss of symmetry and irregular lateral motion of the lateral ventricles are seen in the displacement maps.</p>
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11 pages, 3188 KiB  
Article
Synthesis and Characterization of Iron–Sillenite for Application as an XRD/MRI Dual-Contrast Agent
by Diana Vistorskaja, Jen-Chang Yang, Yu-Tzu Wu, Liang-Yu Chang, Po-Wen Lu, Aleksej Zarkov, Inga Grigoraviciute and Aivaras Kareiva
Crystals 2024, 14(8), 706; https://doi.org/10.3390/cryst14080706 - 5 Aug 2024
Viewed by 778
Abstract
In the present work, iron–sillenite (Bi25FeO40) was synthesized using a simple solid-state reaction method and characterized. The effects of the synthesis conditions on the phase purity of Bi2O3/Fe3O4, morphological features, and [...] Read more.
In the present work, iron–sillenite (Bi25FeO40) was synthesized using a simple solid-state reaction method and characterized. The effects of the synthesis conditions on the phase purity of Bi2O3/Fe3O4, morphological features, and possible application as an XRD/MRI dual-contrast agent were investigated. For the synthesis, the stoichiometric amounts of Bi2O3 and Fe3O4 were mixed and subsequently milled in a planetary ball mill for 10 min with a speed of 300 rpm. The milled mixture was calcined at various temperatures (550 °C, 700 °C, 750 °C, 800 °C, and 850 °C) for 1 h in air at a heating rate of 5 °C/min. For phase identification, powder X-ray diffraction (XRD) analysis was performed and infrared (FTIR) spectra were recorded. The surface morphology of synthesized samples was studied by field-emission scanning electron microscopy (FE-SEM). For the radiopacity measurements, iron–sillenite specimens were synthesized at different temperatures and mixed with different amounts of BaSO4 and Laponite solution. It was demonstrated that iron–sillenite Bi25FeO40 possessed sufficient radiopacity and could be a potential candidate to meet the requirements of its application as an XRD/MRI dual-contrast agent. Full article
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<p>Solid-state reaction synthesis of Bi<sub>25</sub>FeO<sub>40</sub>.</p>
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<p>XRD patterns of Bi<sub>25</sub>FeO<sub>40</sub> synthesis products obtained at 700 °C, 750 °C, and 800 °C. Vertical lines represent the standard XRD pattern of Bi<sub>25</sub>FeO<sub>40</sub>.</p>
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<p>FTIR spectra of Bi<sub>25</sub>FeO<sub>40</sub> synthesis products obtained at 700 °C, 750 °C, and 800 °C.</p>
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<p>SEM micrographs of Bi<sub>25</sub>FeO<sub>40</sub> synthesis products obtained at different temperatures (<b>a</b>) 550 °C; (<b>b</b>) 700 °C; (<b>c</b>) 750 °C; (<b>d</b>) 850 °C.</p>
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<p>Photos of reference samples prepared after 1 h and 12 h showing the stability of prepared reference materials.</p>
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<p>Photos of samples with iron–sillenite prepared after 1 h and 12 h.</p>
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<p>Radiographs of iron–sillenite Bi<sub>25</sub>FeO<sub>40</sub> specimens mixed with BaSO<sub>4</sub> and Laponite.</p>
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<p>Grayscale value dependence on Al mm.</p>
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10 pages, 2354 KiB  
Article
Differentiating Well-Differentiated from Poorly-Differentiated HCC: The Potential and the Limitation of Gd-EOB-DTPA in the Presence of Liver Cirrhosis
by Andrea Goetz, Niklas Verloh, Kirsten Utpatel, Claudia Fellner, Janine Rennert, Ingo Einspieler, Michael Doppler, Lukas Luerken, Leona S. Alizadeh, Wibke Uller, Christian Stroszczynski and Michael Haimerl
Diagnostics 2024, 14(15), 1676; https://doi.org/10.3390/diagnostics14151676 - 2 Aug 2024
Viewed by 1002
Abstract
This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of [...] Read more.
This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of imaging by signal intensity (SI) and lesion contrast (C), to surrounding liver parenchyma, and comparing it across distinct groups of patients differentiated based on the histopathological grading of their HCC lesions and the presence of liver cirrhosis. Our results highlighted a significant contrast between well- and poorly-differentiated lesions regarding the lesion contrast in the arterial and late arterial phases. Furthermore, the hepatobiliary phase showed limited diagnostic value in cirrhotic liver parenchyma due to altered pharmacokinetics. Ultimately, our findings underscore the potential of Gd-EOB-DTPA-enhanced MRI as a tool for improving preoperative diagnosis and treatment selection for HCC while emphasizing the need for continued research to overcome the diagnostic complexities posed by the disease. Full article
(This article belongs to the Special Issue Diagnostic and Interventional Radiology of Liver Diseases)
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<p>Contrast response of the liver lesions for the plain, arterial (AP), late atrial (LAP), portal venous (PVP), and hepatobiliary phase (HBP). (<b>a</b>) absolute signal intensities (<b>b</b>) contrast (C). *, <span class="html-italic">p</span> = 0.040; **, <span class="html-italic">p</span> = 0.010.</p>
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<p>Contrast of HCC lesions in relation to cirrhotic (red) and non-cirrhotic (black) liver parenchyma for the plain, arterial (AP), late atrial (LAP), portal venous (PVP), and hepatobiliary phase (HBP). (<b>a</b>) G1. (<b>b</b>) G2/G3.</p>
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<p>Comparison of well-differentiated and poorly-differentiated HCCs in the presence of liver cirrhosis (ISHAK Score 6) in T1 weighted VIBE sequences (phases as indicated): (<b>A</b>) well-differentiated HCC (G1) in liver fibrosis (ISHAK 2), (<b>B</b>) well-differentiated HCC (G1) in liver cirrhosis (ISHAK 6), (<b>C</b>) poorly-differentiated HCC (G2) in normal liver parenchyma (ISHAK 0), (<b>D</b>) poorly-differentiated HCC (G2) in in liver cirrhosis (ISHAK 6).</p>
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12 pages, 951 KiB  
Article
Aneurysmal Wall Enhancement of Non-Ruptured Intracranial Aneurysms after Endovascular Treatment Correlates with Higher Aneurysm Reperfusion Rates, but Only in Large Aneurysms
by Valentin Ladenhauf, Malik Galijasevic, Milovan Regodic, Raimund Helbok, Verena Rass, Christian Freyschlag, Ondra Petr, Johannes Deeg, Leonhard Gruber, Stephanie Mangesius, Elke Ruth Gizewski and Astrid Ellen Grams
Diagnostics 2024, 14(14), 1533; https://doi.org/10.3390/diagnostics14141533 - 16 Jul 2024
Cited by 1 | Viewed by 765
Abstract
Introduction: Aneurysmal wall enhancement (AWE) of non-ruptured sacular intracranial aneurysms (IA) after endovascular treatment (ET) is a frequently observed imaging finding using AWE-sequences in brain magnetic resonance imaging (MRI). So far, its value remains unclear. We aimed to investigate the effect of AWE [...] Read more.
Introduction: Aneurysmal wall enhancement (AWE) of non-ruptured sacular intracranial aneurysms (IA) after endovascular treatment (ET) is a frequently observed imaging finding using AWE-sequences in brain magnetic resonance imaging (MRI). So far, its value remains unclear. We aimed to investigate the effect of AWE on aneurysm reperfusion rates in a longitudinal cohort. Methods: This is a retrospective MRI study over the timespan of up to 5 years, assessing the correlation of increased AWE of non-ruptured IAs and events of aneurysm reperfusion and retreatment, PHASES Score and grade of AWE. T1 SPACE fat saturation (FS) and T1 SE FS blood suppression sequences after contrast administration were used for visual interpretation of increased AWE. The IAs’ sizes were assessed via the biggest diameter. The grade of enhancement was defined in a grading system from grade 1 to grade 3. Results: 127 consecutive non ruptured IA-patients (58.9 ± 9.0 years, 94 female, 33 male) who underwent elective aneurysm occlusion were included. AWE was observed in 40.2% of patients (51/127) after ET, 6 patients already showed AWE before treatment. In large IAs (which were defined as a single maximum diameter of over 7.5 mm), AWE was significantly associated with aneurysm reperfusion in contrast to large aneurysm without AWE). All grades of AWE were significantly associated with reperfusion. Conclusions: Our data suggests that in patients with initially large IAs, AWE is correlated with aneurysm reperfusion. Full article
(This article belongs to the Special Issue Neuropathology, Neuroimaging and Biomarkers in Neurological Disease)
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<p>From left to right: <b>Left</b>: Grade 1 AWE in a middle cerebral artery Aneurysm, showing non-continuous arterial wall semilunar enhancement on the right ventral circumference. <b>Middle</b>: Grade 2 AWE in a basilar artery aneurysm showing continuous arterial wall enhancement without thickening of the vessel wall. <b>Right</b>: Grade 3 AWE in an internal cerebral artery Aneurysm with continuous enhancement and thickening of the vessel wall, the dorsolaterally located enhancing structure in the bottom right corner of the figure corresponds to the pituitary infundibulum.</p>
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<p>Boxplot of the maximum diameter of an IA vs. AWE in patients with and without reperfusion.</p>
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<p>ROC–Curves showing the relation of the sensitivity and specificity of the maximum IA diameter, AWE, PHASES–Score and aneurysm reperfusion.</p>
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9 pages, 798 KiB  
Case Report
Better 90 Minutes Late than Never: Differential Diagnosis on MRI Scanning in a Case of Hepatic Angiosarcoma
by Teodora Anca Albu and Nicoleta Iacob
Life 2024, 14(7), 823; https://doi.org/10.3390/life14070823 - 28 Jun 2024
Cited by 1 | Viewed by 811
Abstract
Primary hepatic angiosarcoma (PHA) is a rare liver malignancy with few studies describing its radiological characteristics. This article aims to assess the imaging features of each of the multiple delayed contrast-enhanced magnetic resonance imaging (MRI) scans, in addition to the conventional MRI protocol, [...] Read more.
Primary hepatic angiosarcoma (PHA) is a rare liver malignancy with few studies describing its radiological characteristics. This article aims to assess the imaging features of each of the multiple delayed contrast-enhanced magnetic resonance imaging (MRI) scans, in addition to the conventional MRI protocol, in a patient with PHA. Standard MRI sequences and a liver protocol were used in the examination of a 71 year-old male with pathologically proven PHA after current imaging evaluation. In addition, the patient underwent transversal and coronal MRI T1-weighted scans at 10 min, 20 min and 90 min after intravenous (IV) administration of gadobenatedimeglumine (Gd-BOPTA). The PHA revealed a variable appearance on MRI, with classic imaging being insufficient in making a reliable diagnosis. Lesions have increased vascularity, which translates into increased IV contrast uptake in the MRI arterial phase, showing progressive and globular enhancement in the portal and parenchymatous phases. On delayed scans, at 10 min after IV administration, the lesions maintained no washout, but slightly began to washout at 20 min post-contrast. However, in the hepatobiliary phase (90 min post-contrast injection), on an MRI T1-weighted sequence, PHA lesions were hypointense, suggesting the absence of hepatocytes, thus indicating high-grade malignancy. This approach proved the conclusion that in a patient with PHA, an extra MRI T1-weighted scan at 90 min post-gadobenatedimeglumine injection can provide helpful information in differential diagnosis. Full article
(This article belongs to the Special Issue Novel Diagnosis and Treatment of Gastrointestinal Disease)
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<p>(<b>A</b>) Native transversal CT incidental findings on hepatic structure with multiple masses; (<b>B</b>) arterial iodate CT scanning showing hypoattenuating masses; (<b>C</b>) venous CT iodate appearance of nodular enhancement.</p>
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<p>(<b>A</b>) T2 HASTE tra shows PHA lesions with a moderately intense signal, occupying almost 60% of the liver tissue. Increased signal intensity on T2 WI may demonstrate the presence of low flow vessels within the tumor; (<b>B</b>) Diffusion b value 800 suggests diffusion restriction; (<b>C</b>) T1 vibe FS tra pre-enhancement displays intermediate signal intensity with invasion of the surrounding tissue; (<b>D</b>) The arterial phase demonstrates high vascularity and perfusion that results in an increased rate of Gb-BOPTA uptake; (<b>E</b>) The venous portal phase exhibits progressive and globular enhancement; (<b>F</b>) The parenchymatous phase reveals heterogeneous enhancement with progressive filling; (<b>G</b>) The 10 min T1 vibe fs tra delayed phase produces no washout status; (<b>H</b>) The 20 min T1 vibe fs tra delayed phase merely exhibited the beginning of slight onset of washout; (<b>I</b>) On the 90 min T1 vibe fs tra delayed phase, the lesions became hypointense, suggesting the absence of hepatocytes; (<b>J</b>) The 10 min T1 vibe fs cor delayed phase; (<b>K</b>) The 20 min T1 vibe fs cor delayed phase; (<b>L</b>) The 90 min T1 vibe fs cor delayed phase.</p>
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33 pages, 7910 KiB  
Review
Update on Renal Cell Carcinoma Diagnosis with Novel Imaging Approaches
by Marie-France Bellin, Catarina Valente, Omar Bekdache, Florian Maxwell, Cristina Balasa, Alexia Savignac and Olivier Meyrignac
Cancers 2024, 16(10), 1926; https://doi.org/10.3390/cancers16101926 - 18 May 2024
Cited by 3 | Viewed by 2816
Abstract
This review highlights recent advances in renal cell carcinoma (RCC) imaging. It begins with dual-energy computed tomography (DECT), which has demonstrated a high diagnostic accuracy in the evaluation of renal masses. Several studies have suggested the potential benefits of iodine quantification, particularly for [...] Read more.
This review highlights recent advances in renal cell carcinoma (RCC) imaging. It begins with dual-energy computed tomography (DECT), which has demonstrated a high diagnostic accuracy in the evaluation of renal masses. Several studies have suggested the potential benefits of iodine quantification, particularly for distinguishing low-attenuation, true enhancing solid masses from hyperdense cysts. By determining whether or not a renal mass is present, DECT could avoid the need for additional imaging studies, thereby reducing healthcare costs. DECT can also provide virtual unenhanced images, helping to reduce radiation exposure. The review then provides an update focusing on the advantages of multiparametric magnetic resonance (MR) imaging performance in the histological subtyping of RCC and in the differentiation of benign from malignant renal masses. A proposed standardized stepwise reading of images helps to identify clear cell RCC and papillary RCC with a high accuracy. Contrast-enhanced ultrasound may represent a promising diagnostic tool for the characterization of solid and cystic renal masses. Several combined pharmaceutical imaging strategies using both sestamibi and PSMA offer new opportunities in the diagnosis and staging of RCC, but their role in risk stratification needs to be evaluated. Although radiomics and tumor texture analysis are hampered by poor reproducibility and need standardization, they show promise in identifying new biomarkers for predicting tumor histology, clinical outcomes, overall survival, and the response to therapy. They have a wide range of potential applications but are still in the research phase. Artificial intelligence (AI) has shown encouraging results in tumor classification, grade, and prognosis. It is expected to play an important role in assessing the treatment response and advancing personalized medicine. The review then focuses on recently updated algorithms and guidelines. The Bosniak classification version 2019 incorporates MRI, precisely defines previously vague imaging terms, and allows a greater proportion of masses to be placed in lower-risk classes. Recent studies have reported an improved specificity of the higher-risk categories and better inter-reader agreement. The clear cell likelihood score, which adds standardization to the characterization of solid renal masses on MRI, has been validated in recent studies with high interobserver agreement. Finally, the review discusses the key imaging implications of the 2017 AUA guidelines for renal masses and localized renal cancer. Full article
(This article belongs to the Special Issue Updates on Imaging of Common Urogenital Neoplasms)
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<p>Dual-energy CT aspect of a hypervascularized clear cell renal cell carcinoma of the upper pole of the right kidney. (<b>a</b>) Virtual unenhanced image. Note the presence of a solid exophytic renal mass in the upper pole of the right kidney. (<b>b</b>) The lesion enhances during the corticomedullary phase; measurement of the iodine concentration of the lesion (4.9 mg/mL) compared to that of the renal cortex (4.2 mg/mL) during the corticomedullary phase. (<b>c</b>) Monoenergetic image obtained at 40 keV during the nephrographic phase. Note the decrease in iodine concentration of the lesion (4.42 mg/mL) compared to that of the renal cortex (6.1 mg/mL). (<b>d</b>) Monoenergetic image obtained at 70 keV during the excretory phase. Compared to the monoenergetic image at 40 keV, the contrast between the lesion and the adjacent renal cortex is reduced. Note the washout of the lesion (iodine content: 1.8 mg/mL).</p>
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<p>Dual-energy CT aspect of a hypervascularized clear cell renal cell carcinoma of the upper pole of the right kidney. (<b>a</b>) Virtual unenhanced image. Note the presence of a solid exophytic renal mass in the upper pole of the right kidney. (<b>b</b>) The lesion enhances during the corticomedullary phase; measurement of the iodine concentration of the lesion (4.9 mg/mL) compared to that of the renal cortex (4.2 mg/mL) during the corticomedullary phase. (<b>c</b>) Monoenergetic image obtained at 40 keV during the nephrographic phase. Note the decrease in iodine concentration of the lesion (4.42 mg/mL) compared to that of the renal cortex (6.1 mg/mL). (<b>d</b>) Monoenergetic image obtained at 70 keV during the excretory phase. Compared to the monoenergetic image at 40 keV, the contrast between the lesion and the adjacent renal cortex is reduced. Note the washout of the lesion (iodine content: 1.8 mg/mL).</p>
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<p>Dual-energy CT aspect of a hypervascularized clear cell renal cell carcinoma of the upper pole of the right kidney. (<b>a</b>) Virtual unenhanced image. Note the presence of a solid exophytic renal mass in the upper pole of the right kidney. (<b>b</b>) The lesion enhances during the corticomedullary phase; measurement of the iodine concentration of the lesion (4.9 mg/mL) compared to that of the renal cortex (4.2 mg/mL) during the corticomedullary phase. (<b>c</b>) Monoenergetic image obtained at 40 keV during the nephrographic phase. Note the decrease in iodine concentration of the lesion (4.42 mg/mL) compared to that of the renal cortex (6.1 mg/mL). (<b>d</b>) Monoenergetic image obtained at 70 keV during the excretory phase. Compared to the monoenergetic image at 40 keV, the contrast between the lesion and the adjacent renal cortex is reduced. Note the washout of the lesion (iodine content: 1.8 mg/mL).</p>
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<p>Oncocytoma in the right kidney of a 42-year-old man. (<b>A</b>) On the unenhanced image, the 4.8 cm lesion is isodense relative to the renal parenchyma. Enhancement is seen on the corticomedullary phase image (<b>B</b>), followed by washout on the nephrographic (<b>C</b>) and excretory (<b>D</b>) phase images. (<b>E</b>) Macroscopic view of the lesion after radical nephrectomy. Courtesy of Pr S. Ferlicot, Department of Pathology, Bicêtre.</p>
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<p>Oncocytoma in the right kidney of a 42-year-old man. (<b>A</b>) On the unenhanced image, the 4.8 cm lesion is isodense relative to the renal parenchyma. Enhancement is seen on the corticomedullary phase image (<b>B</b>), followed by washout on the nephrographic (<b>C</b>) and excretory (<b>D</b>) phase images. (<b>E</b>) Macroscopic view of the lesion after radical nephrectomy. Courtesy of Pr S. Ferlicot, Department of Pathology, Bicêtre.</p>
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<p>Oncocytoma in the right kidney of a 42-year-old man. (<b>A</b>) On the unenhanced image, the 4.8 cm lesion is isodense relative to the renal parenchyma. Enhancement is seen on the corticomedullary phase image (<b>B</b>), followed by washout on the nephrographic (<b>C</b>) and excretory (<b>D</b>) phase images. (<b>E</b>) Macroscopic view of the lesion after radical nephrectomy. Courtesy of Pr S. Ferlicot, Department of Pathology, Bicêtre.</p>
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<p>CT aspect of a chromophobe renal cell carcinoma in the left kidney of a 68-year-old-woman. (<b>A</b>) Unenhanced image. Presence of an isodense, homogeneous solid lesion at the medium part of the left kidney. (<b>B</b>) It appears moderately hypervascularized on the corticomedullary phase image, with hyperdense septa. (<b>C</b>) There is progressive washout on the nephrographic phase image and the lesions appears hypodense relative to the renal parenchyma (<b>C</b>). (<b>D</b>) Macroscopic view of the lesion after partial nephrectomy. Courtesy of Pr S. Ferlicot, Department of Pathology, Bicêtre Hospital.</p>
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<p>CT aspect of a chromophobe renal cell carcinoma in the left kidney of a 68-year-old-woman. (<b>A</b>) Unenhanced image. Presence of an isodense, homogeneous solid lesion at the medium part of the left kidney. (<b>B</b>) It appears moderately hypervascularized on the corticomedullary phase image, with hyperdense septa. (<b>C</b>) There is progressive washout on the nephrographic phase image and the lesions appears hypodense relative to the renal parenchyma (<b>C</b>). (<b>D</b>) Macroscopic view of the lesion after partial nephrectomy. Courtesy of Pr S. Ferlicot, Department of Pathology, Bicêtre Hospital.</p>
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<p>Multiphasic CT enhancement of a papillary renal cell carcinoma in the middle part of the right kidney of a 63-year-old woman. (<b>A</b>) Mean unenhanced attenuation was 35 HU. (<b>B</b>) Mean corticomedullary phase attenuation was 45 HU. (<b>C</b>) Mean nephrographic phase attenuation was 59 HU. (<b>D</b>) Mean excretory phase attenuation was 65 HU.</p>
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<p>Multiphasic CT enhancement of a papillary renal cell carcinoma in the middle part of the right kidney of a 63-year-old woman. (<b>A</b>) Mean unenhanced attenuation was 35 HU. (<b>B</b>) Mean corticomedullary phase attenuation was 45 HU. (<b>C</b>) Mean nephrographic phase attenuation was 59 HU. (<b>D</b>) Mean excretory phase attenuation was 65 HU.</p>
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<p>Clear cell renal cell carcinoma in the right kidney of a 52-year-old-man. (<b>A</b>) Coronal T2-weighted fast SE image shows a large heterogeneous mass with areas of high signal intensity compared with renal parenchyma. Transverse in-phase (<b>B</b>,<b>C</b>) opposed-phase MR images show a subtle signal loss on the opposed-phase image. (<b>D</b>) The ADC map is heterogeneous with predominant areas of restriction of tumor diffusion. Transverse gadolinium-enhanced T1-weighted gradient-echo spoiled MR images in (<b>E</b>) corticomedullary, (<b>F</b>) nephrographic, (<b>G</b>) and delayed phase images show intense and rapid peripheral enhancement during the arterial and nephrographic phases followed by a rapid washout of contrast on the delayed phase. Central necrotic areas do not enhance. (<b>H</b>) Macroscopic view of the lesion after radical nephrectomy. The lesion appears heterogeneous. Courtesy of Pr S. Ferlicot, Department of Pathology, Bicêtre Hospital.</p>
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<p>Clear cell renal cell carcinoma in the right kidney of a 52-year-old-man. (<b>A</b>) Coronal T2-weighted fast SE image shows a large heterogeneous mass with areas of high signal intensity compared with renal parenchyma. Transverse in-phase (<b>B</b>,<b>C</b>) opposed-phase MR images show a subtle signal loss on the opposed-phase image. (<b>D</b>) The ADC map is heterogeneous with predominant areas of restriction of tumor diffusion. Transverse gadolinium-enhanced T1-weighted gradient-echo spoiled MR images in (<b>E</b>) corticomedullary, (<b>F</b>) nephrographic, (<b>G</b>) and delayed phase images show intense and rapid peripheral enhancement during the arterial and nephrographic phases followed by a rapid washout of contrast on the delayed phase. Central necrotic areas do not enhance. (<b>H</b>) Macroscopic view of the lesion after radical nephrectomy. The lesion appears heterogeneous. Courtesy of Pr S. Ferlicot, Department of Pathology, Bicêtre Hospital.</p>
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<p>Fat-poor angiomyolipoma in the right kidney of a 46-year-old-man. (<b>A</b>) Coronal T2-weighted fast SE image shows the low signal intensity of the lesion compared with the renal parenchyma. Transverse in-phase (<b>B</b>,<b>C</b>) opposed-phase MR images show a significant loss of signal intensity on the opposed-phase image. (<b>D</b>) The ADC map shows marked restriction of tumor diffusion into the renal mass. Transverse gadolinium-enhanced T1-weighted gradient-echo spoiled MR images in (<b>E</b>) corticomedullary, (<b>F</b>) nephrographic, (<b>G</b>) and delayed phase images show early enhancement and rapid washout.</p>
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<p>Fat-poor angiomyolipoma in the right kidney of a 46-year-old-man. (<b>A</b>) Coronal T2-weighted fast SE image shows the low signal intensity of the lesion compared with the renal parenchyma. Transverse in-phase (<b>B</b>,<b>C</b>) opposed-phase MR images show a significant loss of signal intensity on the opposed-phase image. (<b>D</b>) The ADC map shows marked restriction of tumor diffusion into the renal mass. Transverse gadolinium-enhanced T1-weighted gradient-echo spoiled MR images in (<b>E</b>) corticomedullary, (<b>F</b>) nephrographic, (<b>G</b>) and delayed phase images show early enhancement and rapid washout.</p>
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<p>Papillary renal cell carcinoma in the right kidney of a 75-year-old-woman. (<b>A</b>) Axial T2-weighted fast SE image shows a homogeneous 1.8 cm mass in the posterolateral region of the right kidney, with a lower SI compared to renal parenchyma. Transverse in-phase (<b>B</b>,<b>C</b>) opposed-phase MR images do not show a significant signal loss on the opposed-phase image. (<b>D</b>) The ADC map shows restriction of tumor diffusion into the renal mass. Transverse nonenhanced (<b>E</b>) and gadolinium-enhanced T1-weighted gradient-echo spoiled MR images in (<b>F</b>) corticomedullary, (<b>G</b>) nephrographic, (<b>H</b>) and delayed phase images show progressive enhancement without washout; the mass is hypovascular compared to the renal cortex.</p>
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<p>Papillary renal cell carcinoma in the right kidney of a 75-year-old-woman. (<b>A</b>) Axial T2-weighted fast SE image shows a homogeneous 1.8 cm mass in the posterolateral region of the right kidney, with a lower SI compared to renal parenchyma. Transverse in-phase (<b>B</b>,<b>C</b>) opposed-phase MR images do not show a significant signal loss on the opposed-phase image. (<b>D</b>) The ADC map shows restriction of tumor diffusion into the renal mass. Transverse nonenhanced (<b>E</b>) and gadolinium-enhanced T1-weighted gradient-echo spoiled MR images in (<b>F</b>) corticomedullary, (<b>G</b>) nephrographic, (<b>H</b>) and delayed phase images show progressive enhancement without washout; the mass is hypovascular compared to the renal cortex.</p>
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<p>Same lesion as <a href="#cancers-16-01926-f003" class="html-fig">Figure 3</a>. Chromophobe renal cell carcinoma in the left kidney of a 68-year-old-woman. (<b>A</b>) Axial T2-weighted fast SE image shows the exophytic heterogeneous isointense renal mass with a posterior hyperintense area. Transverse in-phase (<b>B</b>,<b>C</b>) opposed-phase MR images show no significant loss of signal intensity on the opposed-phase image. (<b>D</b>) The ADC map shows restriction of tumor diffusion into the renal mass. Transverse nonenhanced (<b>E</b>) and gadolinium-enhanced T1-weighted gradient-echo spoiled MR images in (<b>F</b>) corticomedullary, (<b>G</b>) nephrographic, (<b>H</b>) and delayed phase images show a mid-intense enhancement of the lesion without visible washout.</p>
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<p>Same lesion as <a href="#cancers-16-01926-f003" class="html-fig">Figure 3</a>. Chromophobe renal cell carcinoma in the left kidney of a 68-year-old-woman. (<b>A</b>) Axial T2-weighted fast SE image shows the exophytic heterogeneous isointense renal mass with a posterior hyperintense area. Transverse in-phase (<b>B</b>,<b>C</b>) opposed-phase MR images show no significant loss of signal intensity on the opposed-phase image. (<b>D</b>) The ADC map shows restriction of tumor diffusion into the renal mass. Transverse nonenhanced (<b>E</b>) and gadolinium-enhanced T1-weighted gradient-echo spoiled MR images in (<b>F</b>) corticomedullary, (<b>G</b>) nephrographic, (<b>H</b>) and delayed phase images show a mid-intense enhancement of the lesion without visible washout.</p>
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<p>Same lesion as <a href="#cancers-16-01926-f002" class="html-fig">Figure 2</a>. Oncocytoma in the right kidney of a 42-year-old man. (<b>A</b>) The axial T2-weighted fast SE image shows a heterogeneous lesion with a central hyperintense area. Transverse in-phase (<b>B</b>,<b>C</b>) opposed-phase MR images show no significant loss of signal intensity on the opposed-phase image. (<b>D</b>) The lesion is hyperintense on the diffusion-weighted image. Transverse nonenhanced (<b>E</b>) and gadolinium-enhanced T1-weighted gradient-echo spoiled MR images in (<b>F</b>) corticomedullary, (<b>G</b>) nephrographic, (<b>H</b>) and delayed phase images show early enhancement and rapid washout.</p>
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<p>Same lesion as <a href="#cancers-16-01926-f002" class="html-fig">Figure 2</a>. Oncocytoma in the right kidney of a 42-year-old man. (<b>A</b>) The axial T2-weighted fast SE image shows a heterogeneous lesion with a central hyperintense area. Transverse in-phase (<b>B</b>,<b>C</b>) opposed-phase MR images show no significant loss of signal intensity on the opposed-phase image. (<b>D</b>) The lesion is hyperintense on the diffusion-weighted image. Transverse nonenhanced (<b>E</b>) and gadolinium-enhanced T1-weighted gradient-echo spoiled MR images in (<b>F</b>) corticomedullary, (<b>G</b>) nephrographic, (<b>H</b>) and delayed phase images show early enhancement and rapid washout.</p>
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<p>Papillary renal cell carcinoma in the right kidney of a 54-year-old woman. (<b>A</b>) B-mode ultrasound shows a large right cystic renal mass with heterogeneous contents and a dependent sediment. (<b>B</b>) CEUS with Sonovue<sup>®</sup> (Bracco Imaging France, Massy, France) reveals the presence of a solid enhancing component at the posterior aspect of the mass. (<b>C</b>) The mass was resected. Pathology identified a necrotic papillary renal cell carcinoma. Courtesy of Pr S. Ferlicot, Department of Pathology, Bicêtre Hospital.</p>
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<p>Papillary renal cell carcinoma in the right kidney of a 54-year-old woman. (<b>A</b>) B-mode ultrasound shows a large right cystic renal mass with heterogeneous contents and a dependent sediment. (<b>B</b>) CEUS with Sonovue<sup>®</sup> (Bracco Imaging France, Massy, France) reveals the presence of a solid enhancing component at the posterior aspect of the mass. (<b>C</b>) The mass was resected. Pathology identified a necrotic papillary renal cell carcinoma. Courtesy of Pr S. Ferlicot, Department of Pathology, Bicêtre Hospital.</p>
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17 pages, 9206 KiB  
Article
Contrast Agent Dynamics Determine Radiomics Profiles in Oncologic Imaging
by Martin L. Watzenboeck, Lucian Beer, Daria Kifjak, Sebastian Röhrich, Benedikt H. Heidinger, Florian Prayer, Ruxandra-Iulia Milos, Paul Apfaltrer, Georg Langs, Pascal A. T. Baltzer and Helmut Prosch
Cancers 2024, 16(8), 1519; https://doi.org/10.3390/cancers16081519 - 16 Apr 2024
Viewed by 1250
Abstract
Background: The reproducibility of radiomics features extracted from CT and MRI examinations depends on several physiological and technical factors. The aim was to evaluate the impact of contrast agent timing on the stability of radiomics features using dynamic contrast-enhanced perfusion CT (dceCT) or [...] Read more.
Background: The reproducibility of radiomics features extracted from CT and MRI examinations depends on several physiological and technical factors. The aim was to evaluate the impact of contrast agent timing on the stability of radiomics features using dynamic contrast-enhanced perfusion CT (dceCT) or MRI (dceMRI) in prostate and lung cancers. Methods: Radiomics features were extracted from dceCT or dceMRI images in patients with biopsy-proven peripheral prostate cancer (pzPC) or biopsy-proven non-small cell lung cancer (NSCLC), respectively. Features that showed significant differences between contrast phases were identified using linear mixed models. An L2-penalized logistic regression classifier was used to predict class labels for pzPC and unaffected prostate regions-of-interest (ROIs). Results: Nine pzPC and 28 NSCLC patients, who were imaged with dceCT and/or dceMRI, were included in this study. After normalizing for individual enhancement patterns by defining seven individual phases based on a reference vessel, 19, 467 and 128 out of 1204 CT features showed significant temporal dynamics in healthy prostate parenchyma, prostate tumors and lung tumors, respectively. CT radiomics-based classification accuracy of healthy and tumor ROIs was highly dependent on contrast agent phase. For dceMRI, 899 and 1027 out of 1118 features were significantly dependent on time after contrast agent injection for prostate and lung tumors. Conclusions: CT and MRI radiomics features in both prostate and lung tumors are significantly affected by interindividual differences in contrast agent dynamics. Full article
(This article belongs to the Topic AI in Medical Imaging and Image Processing)
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<p>Synchronization of CT image series across prostate cancer patients. (<b>A</b>) Median voxel intensity as a function of time for each of the seven pzPC patients who were imaged with dceCT after intravenous injection of contrast medium. Lines are colored according to patients. (<b>B</b>) Definition of seven contrast agent phases on a single patient, to enable synchronization of image series across patients. (<b>C</b>) Representative slices for the seven defined contrast agent phases of a single prostate cancer patient.</p>
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<p>Significantly affected CT radiomics features in healthy prostate tissue and pzPC. (<b>A</b>) Heatmap of arterial lumen median voxel intensity. (<b>B</b>,<b>C</b>) Heatmaps of radiomics features with significant temporal dynamics after intravenous contrast agent injection for healthy prostate parenchyma (<b>B</b>) and pzPC (<b>C</b>) sections. For each feature, mean values for all seven patients were z-score transformed over the seven timepoints. Features are grouped according to hierarchical clustering, which is represented by dendrograms. (<b>D</b>,<b>E</b>) Number of radiomics features with and without significant temporal dynamics, grouped by feature class and colored according to clusters as defined in (<b>B</b>,<b>C</b>). glcm: gray level co-occurrence matrix, gldm: gray level dependence matrix, glrlm: gray level run length matrix, glszm: gray level size zone matrix.</p>
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<p>Machine-learning-based classification of healthy and pzPC ROIs depends on contrast agent phase. (<b>A</b>) ROC curves for logistic regression classifiers with an L2 penalty differentiating between healthy and tumor ROIs. Numbering above the curves denotes the timepoint after contrast agent injection. (<b>B</b>) AUC and 95% confidence intervals for each timepoint, which is represented on the <span class="html-italic">x</span>-axis. ROI, region-of-interest; pzPC, peripheral zone prostate cancer; TPR, true-positive rate; FPR, false-positive rate.</p>
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<p>CT radiomics feature dynamics in lung cancer. (<b>A</b>) Representative slices for the seven defined contrast agent phases of a single lung cancer patient. (<b>B</b>) Heatmap of aortal lumen median voxel intensity. (<b>C</b>) Heatmap of radiomics features with significant temporal dynamics after intravenous contrast agent injection in solid lung tumors. For each feature, mean values for all seven patients are z-score transformed over the seven timepoints. Features are grouped by hierarchical clustering. (<b>D</b>) Distribution of radiomics features across different feature classes. Features are colored according to clusters defined in (<b>C</b>). glcm: gray level co-occurrence matrix, gldm: gray level dependence matrix, glrlm: gray level run length matrix, glszm: gray level size zone matrix.</p>
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<p>MRI radiomics feature dynamics in prostate cancer. (<b>A</b>) Representative slice illustrating segmentation of femoral artery and pzPC lesions in a single pzPC patient. (<b>B</b>) Heatmap of the femoral artery lumen median voxel intensity. (<b>C</b>) Heatmap of radiomics features with significant temporal dynamics after intravenous contrast agent injection in pzPC lesions. Features are grouped by hierarchical clustering. (<b>D</b>) Distribution of radiomics features across different feature classes. Features are colored according to clusters defined in (<b>C</b>). glcm: gray level co-occurrence matrix, gldm: gray level dependence matrix, glrlm: gray level run length matrix, glszm: gray level size zone matrix.</p>
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<p>MRI radiomics feature dynamics in lung cancer. (<b>A</b>) Representative slice illustrating segmentation of thoracic aorta and NSCLC lesions in a single NSCLC patient. (<b>B</b>) Heatmap of aortal lumen median voxel intensity. (<b>C</b>) Heatmap of radiomics features with significant temporal dynamics after intravenous contrast agent injection in solid lung tumors. Features are grouped by hierarchical clustering. (<b>D</b>) Distribution of radiomics features across different feature classes. Features are colored according to clusters defined in (<b>C</b>). glcm: gray level co-occurrence matrix, gldm: gray level dependence matrix, glrlm: gray level run length matrix, glszm: gray level size zone matrix.</p>
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10 pages, 3315 KiB  
Communication
Contrast Clearance Analysis (CCA) to Assess Viable Tumour following Stereotactic Radiosurgery (SRS) to Brain Metastasis in Non-Small Cell Lung Cancer (NSCLC)
by Shybi Mohamedkhan, Sumeet Hindocha, James de Boisanger, Thomas Millard, Liam Welsh, Philip Rich, Andrew D. MacKinnon, Nicholas Williams, Bhupinder Sharma, Nicola Rosenfelder and Anna Minchom
Cancers 2024, 16(6), 1218; https://doi.org/10.3390/cancers16061218 - 20 Mar 2024
Cited by 2 | Viewed by 1725
Abstract
Background and Objective: Brain metastases are common in lung cancer and increasingly treated using targeted radiotherapy techniques such as stereotactic radiosurgery (SRS). Using MRI, post-SRS changes may be difficult to distinguish from progressive brain metastasis. Contrast clearance analysis (CCA) uses T1-weighted MRI images [...] Read more.
Background and Objective: Brain metastases are common in lung cancer and increasingly treated using targeted radiotherapy techniques such as stereotactic radiosurgery (SRS). Using MRI, post-SRS changes may be difficult to distinguish from progressive brain metastasis. Contrast clearance analysis (CCA) uses T1-weighted MRI images to assess the clearance of gadolinium and can be thus used to assess vascularity and active tumours. Design and Methods: We retrospectively assessed CCAs in 62 patients with non-small cell lung cancer (NSCLC) undergoing 104 CCA scans in a single centre. Results: The initial CCA suggested the aetiology of equivocal changes on standard MRI in 80.6% of patients. In all patients whose initial CCA showed post-SRS changes and who underwent serial CCAs, the initial diagnosis was upheld with the serial imaging. In only two cases of a presumed progressive tumour on the initial CCA, subsequent treatment for radionecrosis was instigated; a retrospective review and re-evaluation of the CCAs show that progression was reported where a thin rim of rapid contrast clearance was seen, and this finding has been subsequently recognised as a feature of post-treatment change on CCAs. The lack of concordance with CCA findings in those who underwent surgical resection was also found to be due to the over-reporting of the thin blue rim as disease in the early cases of CCA use and, in three cases, potentially related to timelines longer than 7 days prior to surgery, both factors being unknown during the early implementation phase of CCA at our centre but subsequently learned. Conclusions: Our single-centre experience shows CCA to be feasible and useful in patients with NSCLC in cases of diagnostic uncertainty in MRI. It has helped guide treatment in the majority of patients, with subsequent outcomes following the implementation of the treatment based on the results, suggesting correct classification. Recommendations from our experience of the implementation include the careful consideration of the thin rim of the rapid contrast clearance and the timing of the CCA prior to surgery for suspected brain metastasis progression. Full article
(This article belongs to the Section Methods and Technologies Development)
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<p>Outcomes following initial CCA scan (subsequent CCA outcomes not shown). SACT: systemic anti-cancer therapy, SRS: stereotactic radiosurgery.</p>
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<p>Case study of patient undergoing CCA demonstrating “thin blue rim” (arrowed) around tumour bed.</p>
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<p>Case study of patient undergoing serial CCAs for suspected brain metastatic growth. CCA: contrast clearance analysis, Gy: grey, NSCLC: non-small cell lung cancer, SRS: stereotactic radiosurgery.</p>
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