Artifact reduction of coaxial needles in magnetic resonance imaging-guided abdominal interventions at 1.5 T: a phantom study

Needle artifacts pose a major limitation for MRI-guided interventions, as they impact the visually perceived needle size and needle-to-target-distance. The objective of this agar liver phantom study was to establish an experimental basis to understand and reduce needle artifact formation during MRI-guided abdominal interventions. Using a vendor-specific prototype fluoroscopic T1-weighted gradient echo sequence with real-time multiplanar acquisition at 1.5~T, the influence of 6 parameters (flip angle, bandwidth, matrix, slice thickness, read-out direction, intervention angle relative to B0) on artifact formation of 4 different coaxial MR-compatible coaxial needles (Nitinol, 16G-22G) was investigated. As one parameter was modified, the others remained constant. For each individual parameter variation, 2 independent and blinded readers rated artifact diameters at 2 predefined positions (15~mm distance from the perceived needle tip and at 50% of the needle length). Differences between the experimental subgroups were assessed by Bonferroni-corrected non-parametric tests. Correlations between continuous variables were expressed by the Bravais-Pearson coefficient and interrater reliability was quantified using the intraclass classification coefficient. Needle artifact size increased gradually with increasing flip angles (p = 0.002) as well as increasing intervention angles (p < 0.001). Artifact diameters differed significantly between the chosen matrix sizes (p = 0.002) while modifying bandwidth, readout direction, and slice thickness showed no significant differences. Interrater reliability was high (intraclass correlation coefficient 0.776-0.910). To minimize needle artifacts in MRI-guided abdominal interventions while maintaining optimal visibility of the coaxial needle, we suggest medium-range flip angles and low intervention angles relative to B0

Optimized visualization of focal liver lesions and vascular structures in real-time T1-weighted gradient echo sequences for magnetic resonance-guided liver procedures

PURPOSEThis study aimed to determine the optimal sequence parameters of a real-time T1-weighted (T1w) gradient echo (GRE) sequence for magnetic resonance (MR)-guided liver interventions.METHODSWe included 94 patients who underwent diagnostic liver MR imaging (MRI) and acquired additional real-time T1w GRE sequences with a closed 1.5-T MRI scanner 20 min after a liver-specific contrast agent was injected. In four measurement series, one of the following four sequence parameters was changed, and repeated scans with different values for this parameter were acquired: flip angle (FA) (10–90°), repetition time (TR) (5.47–8.58 ms), bandwidth (BW) (300–700 Hz/pixel), and matrix (96 × 96–256 × 256). Two readers rated the visualizations of the target and risk structures (7-point Likert scale) and the extent of artifacts (6-point Likert scale); they also quantified the lesion–liver contrast ratio, the lesion–liver contrast-to-noise ratio (CNR), and the liver signal-to-noise ratio (SNR). Substratification analyses were performed for differences in overall visual and quantitative assessments depending on the lesion size, type, and the presence of cirrhosis.RESULTSFor the utilized FAs and matrix sizes, significant differences were found in the visual assessments of the conspicuity of target lesions, risk structures, and the extent of artifacts as well as in the quantitative assessments of lesion–liver contrast ratios and liver SNRs (all P < 0.001). No differences were observed for modified TR and BW. Significantly increased conspicuity of the target and vascular structures was observed for both higher FAs and matrix sizes, while the ghosting artifacts increased and decreased, respectively. For primary liver tumors compared with metastatic lesions, and for cirrhotic livers compared with normal liver parenchyma, significantly decreased conspicuity of the target lesions (P = 0.005, P = 0.005), lesion–liver CNRs (P = 0.005, P = 0.032), and lesion–liver contrast ratios (P = 0.015, P = 0.032) were found. All results showed no significant correlation with lesion size.CONCLUSIONWe recommend an FA of 30°–45° and a matrix size of 128 × 128–192 × 192 for MR-guided liver interventions with real-time T1w sequences to provide a balance between good visualizations of target and risk structures, high signal intensities, and low ghosting artifacts. The visualization of the target lesion may vary due to clinical conditions, such as lesion type or associated chronic liver disease

Monitoring Cell Death in Regorafenib-Treated Experimental Colon Carcinomas Using Annexin-Based Optical Fluorescence Imaging Validated by Perfusion MRI

Objective To investigate annexin-based optical fluorescence imaging (OI) for monitoring regorafenib-induced early cell death in experimental colon carcinomas in rats, validated by perfusion MRI and multiparametric immunohistochemistry. Materials and Methods Subcutaneous human colon carcinomas (HT-29) in athymic rats (n = 16) were imaged before and after a one-week therapy with regorafenib (n = 8) or placebo (n = 8) using annexin-based OI and perfusion MRI at 3 Tesla. Optical signal-to-noise ratio (SNR) and MRI tumor perfusion parameters (plasma flow PF, mL/100mL/min;plasma volume PV,%) were assessed. On day 7, tumors underwent immunohistochemical analysis for tumor cell apoptosis (TUNEL),proliferation (Ki-67),and microvascular density (CD31). Results Apoptosis-targeted OI demonstrated a tumor-specific probe accumulation with a significant increase of tumor SNR under therapy (mean Delta +7.78 +/- 2.95, control: -0.80 +/- 2.48, p = 0.021). MRI detected a significant reduction of tumor perfusion in the therapy group (mean Delta PF -8.17 +/- 2.32 mL/100 mL/min, control -0.11 +/- 3.36 mL/100 mL/min, p = 0.036). Immunohistochemistry showed significantly more apoptosis (TUNEL;11392 +/- 1486 vs. 2921 +/- 334, p = 0.001),significantly less proliferation (Ki-67;1754 +/- 184 vs. 2883 +/- 323, p = 0.012),and significantly lower microvascular density (CD31;107 +/- 10 vs. 182 +/- 22, p = 0.006) in the therapy group. Conclusions Annexin-based OI allowed for the non-invasive monitoring of regorafenib-induced early cell death in experimental colon carcinomas, validated by perfusion MRI and multiparametric immunohistochemistry

Non-Contrast-Enhanced MR Angiography at 3 Tesla in Patients with Advanced Peripheral Arterial Occlusive Disease

Purpose: The aim of this study was to assess the diagnostic performance of ECG-gated non-contrast-enhanced quiescent interval single-shot (QISS) magnetic resonance angiography at a magnetic field strength of 3 Tesla in patients with advanced peripheral arterial occlusive disease (PAOD). Method and Materials: A total of 21 consecutive patients with advanced PAOD (Fontaine stage IIb and higher) referred for peripheral magnetic resonance angiography (MRA) were included. Imaging was performed on a 3 T whole body MR. Image quality and stenosis diameter were evaluated in comparison to contrast-enhanced continuous table and TWIST MRA (CE-MRA) as standard of reference. QISS images were acquired with a thickness of 1.5 mm each (high-resolution QISS, HR-QISS). Two blinded readers rated the image quality and the degree of stenosis for both HR-QISS and CE-MRA in 26 predefined arterial vessel segments on 5-point Likert scales. Results: With CE-MRA as the reference standard, HR-QISS showed high sensitivity (94.1%),specificity (97.8%),positive (95.1%),and negative predictive value (97.2%) for the detection of significant (>= 50%) stenosis. Interreader agreement for stenosis assessment of both HR-QISS and CE-MRA was excellent (kappa-values of 0.951 and 0.962, respectively). As compared to CR-MRA, image quality of HR-QISS was significantly lower for the distal aorta, the femoral and iliac arteries (each with p<0.01),while no significant difference was found in the popliteal (p = 0.09) and lower leg arteries (p = 0.78). Conclusion: Non-enhanced ECG-gated HR-QISS performs very well in subjects with severe PAOD and is a good alternative for patients with a high risk of nephrogenic systemic fibrosis

Contrast-Enhanced Ultrasound with VEGFR2-Targeted Microbubbles for Monitoring Regorafenib Therapy Effects in Experimental Colorectal Adenocarcinomas in Rats with DCE-MRI and Immunohistochemical Validation

Objectives To investigate contrast-enhanced ultrasound (CEUS) with VEGFR2-targeted microbubbles for monitoring therapy effects of regorafenib on experimental colon carcinomas in rats with correlation to dynamic contrast-enhanced MRI (DCE-MRI) and immunohistochemistry. Materials and Methods: Human colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n =21 (n = 11 therapy group;n = 10 control group) female athymic nude rats (Hsd: RH-Foxn1 (mu)). Animals were imaged at baseline and after a one-week daily treatment with regorafenib or a placebo (10 mg/kg bodyweight), using CEUS with VEGFR2-targeted microbubbles and DCE-MRI. In CEUS tumor perfusion was assessed during an early vascular phase (wash-in area under the curve = WiAUC) and VEGFR2-specific binding during a late molecular phase (signal intensity after 8 (SI8min) and 10 minutes (SI10min)), using a conventional 15L8 linear transducer (transmit frequency 7 MHz, dynamic range 80 dB, depth 25 mm). In DCE-MRI functional parameters plasma flow (PF) and plasma volume (PV) were quantified. For validation purposes, CEUS parameters were correlated with DCE-MRI parameters and immunohistochemical VEGFR2, CD31, Ki-67 and TUNEL stainings. Results: CEUS perfusion parameter WiAUC decreased significantly (116,989 +/- 77,048 a.u. to 30,076 +/- 27,095a.u.;p = 0.005) under therapy with no significant changes (133,932 +/- 65,960 a.u. to 84,316 +/- 74,144 a.u.;p = 0.093) in the control group. In the therapy group, the amount of bound microbubbles in the late phase was significantly lower in the therapy than in the control group on day 7 (SI8min: 283 +/- 191 vs. 802 +/- 460 a.u.;p = 0.006);SI10min: 226 +/- 149 vs. 645 +/- 461 a.u.;p = 0.009). PF and PV decreased significantly (PF: 147 +/- 58 mL/100 mL/min to 71 +/- 15 mL/100 mL/min;p = 0.003;PV: 13 +/- 3% to 9 +/- 4%;p = 0.040) in the therapy group. Immunohistochemistry revealed significantly fewer VEGFR2 (7.2 +/- 1.8 vs. 17.8 +/- 4.6;p < 0.001), CD31 (8.1 +/- 3.0 vs. 20.8 +/- 5.7;p < 0.001) and Ki-67 (318.7 +/- 94.0 vs. 468.0 +/- 133.8;p = 0.004) and significantly more TUNEL (672.7 +/- 194.0 vs. 357.6 +/- 192.0;p = 0.003) positive cells in the therapy group. CEUS parameters showed significant (p < 0.05) correlations to DCE-MRI parameters and immunohistochemistry. Conclusions CEUS with VEGFR2-targeted microbubbles allowed for monitoring regorafenib functional and molecular therapy effects on experimental colorectal adenocarcinomas with a significant decline of CEUS and DCE-MRI perfusion parameters as well as a significant reduction of specifically bound microbubbles under therapy, consistent with a reduced expression of VEGFR2

Correlation of Perfusion MRI and F-18-FDG PET Imaging Biomarkers for Monitoring Regorafenib Therapy in Experimental Colon Carcinomas with Immunohistochemical Validation

Objectives To investigate a multimodal, multiparametric perfusion MRI/F-18-fluoro-deoxyglucose (F-18-FDG)-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation. Materials and Methods Human colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n = 17 (n = 10 therapy group;n = 7 control group) female athymic nude rats (Hsd: RH-Foxn1(mu)). Animals were imaged at baseline and after a one-week daily treatment protocol with regorafenib (10 mg/kg bodyweight) using a multimodal, multiparametric perfusion MRI/F-18-FDG-PET imaging protocol. In perfusion MRI, quantitative parameters of plasma flow (PF, mL/100 mL/min), plasma volume (PV,%) and endothelial permeability-surface area product (PS, mL/100 mL/min) were calculated. In F-18-FDG-PET, tumor-to-background-ratio (TTB) was calculated. Perfusion MRI parameters were correlated with TTB and immunohistochemical assessments of tumor microvascular density (CD-31) and cell proliferation (Ki-67). Results Regorafenib significantly (p<0.01) suppressed PF (81.1 +/- 7.5 to 50.6 +/- 16.0 mL/100mL/min), PV (12.1 +/- 3.6 to 7.5 +/- 1.6%) and PS (13.6 +/- 3.2 to 7.9 +/- 2.3 mL/100mL/min) as well as TTB (3.4 +/- 0.6 to 1.9 +/- 1.1) between baseline and day 7. Immunohistochemistry revealed significantly (p<0.03) lower tumor microvascular density (CD-31, 7.0 +/- 2.4 vs. 16.1 +/- 5.9) and tumor cell proliferation (Ki-67, 434.0 +/- 62.9 vs. 663.0 +/- 98.3) in the therapy group. Perfusion MRI parameters Delta PF, Delta PV and Delta PS showed strong and significant (r = 0.67-0.78;p<0.01) correlations to the PET parameter Delta TTB and significant correlations (r = 0.57-0.67;p<0.03) to immunohistochemical Ki-67 as well as to CD-31-stainings (r = 0.49-0.55;p<0.05). Conclusions A multimodal, multiparametric perfusion MRI/PET imaging protocol allowed for non-invasive monitoring of regorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant correlations between perfusion MRI parameters and F-18-FDG-PET validated by immunohistochemistry

18F–FDG-PET/CT and diffusion-weighted MRI for monitoring a BRAF and CDK 4/6 inhibitor combination therapy in a murine model of human melanoma

Background: The purpose of the study was to investigate a novel BRAF and CDK 4/6 inhibitor combination therapy in a murine model of BRAF-V600-mutant human melanoma monitored by F-18-FDG-PET/CT and diffusionweighted MRI (DW-MRI). Methods: Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude mice (n = 21) were imaged by 18F-FDG-PET/CT and DW-MRI before (day 0) and after (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12;dabrafenib, 20 mg/kg/d;ribociclib, 100 mg/kg/d) or placebo (n = 9). Animals were scanned on a small animal PET after intravenous administration of 20 MBq F-18-FDG. Tumor glucose uptake was calculated as the tumor-to-liver-ratio (TTL). Unenhanced CT data sets were subsequently acquired for anatomic coregistration. Tumor diffusivity was assessed by DW-MRI using the apparent diffusion coefficient (ADC). Anti-tumor therapy effects were assessed by ex vivo immunohistochemistry for validation purposes (microvascular density -CD31;tumor cell proliferation -Ki-67). Results: Tumor glucose uptake was significantly suppressed under therapy (Delta TTLTherapy -1.00 +/- 0.53 vs.Delta TTLControl 0.85 +/- 1.21;p < 0.001). In addition, tumor diffusivity was significantly elevated following the BRAF and CDK 4/6 inhibitor combination therapy (Delta ADC(Therapy) 0.12 +/- 0.14 x 10(-3) mm(2)/s;Delta ADCControl -0.12 +/- 0.06 x 10(-3) mm(2)/s;p < 0.001). Immunohistochemistry revealed a significant suppression of microvascular density (CD31, 147 +/- 48 vs. 287 +/- 92;p = 0.001) and proliferation (Ki-67, 3718 +/- 998 vs. 5389 +/- 1332;p = 0.007) in the therapy compared to the control group. Conclusion: A novel BRAF and CDK 4/6 inhibitor combination therapy exhibited significant anti-angiogenic and anti-proliferative effects in experimental human melanomas, monitored by F-18-FDG-PET/CT and DW-MRI

Non-contrast-enhanced MR angiography at 3 Tesla in patients with advanced peripheral arterial occlusive disease.

PURPOSE: The aim of this study was to assess the diagnostic performance of ECG-gated non-contrast-enhanced quiescent interval single-shot (QISS) magnetic resonance angiography at a magnetic field strength of 3 Tesla in patients with advanced peripheral arterial occlusive disease (PAOD). METHOD AND MATERIALS: A total of 21 consecutive patients with advanced PAOD (Fontaine stage IIb and higher) referred for peripheral magnetic resonance angiography (MRA) were included. Imaging was performed on a 3 T whole body MR. Image quality and stenosis diameter were evaluated in comparison to contrast-enhanced continuous table and TWIST MRA (CE-MRA) as standard of reference. QISS images were acquired with a thickness of 1.5 mm each (high-resolution QISS, HR-QISS). Two blinded readers rated the image quality and the degree of stenosis for both HR-QISS and CE-MRA in 26 predefined arterial vessel segments on 5-point Likert scales. RESULTS: With CE-MRA as the reference standard, HR-QISS showed high sensitivity (94.1%), specificity (97.8%), positive (95.1%), and negative predictive value (97.2%) for the detection of significant (≥ 50%) stenosis. Interreader agreement for stenosis assessment of both HR-QISS and CE-MRA was excellent (κ-values of 0.951 and 0.962, respectively). As compared to CR-MRA, image quality of HR-QISS was significantly lower for the distal aorta, the femoral and iliac arteries (each with p<0.01), while no significant difference was found in the popliteal (p = 0.09) and lower leg arteries (p = 0.78). CONCLUSION: Non-enhanced ECG-gated HR-QISS performs very well in subjects with severe PAOD and is a good alternative for patients with a high risk of nephrogenic systemic fibrosis

Contrast-enhanced continuous table movement (left) and non-enhanced HR-QISS (right) MRA in a 68 y/o male patient suffering from PAOD stage IV.

<p>The examination was performed after percutaneous transluminal angioplasty (PTA) of the right superficial femoral artery. Both CE-MRA and HR-QISS depict multiple significant (>50%) stenoses in the right superficial femoral artery, an occlusion of the right anterior tibial artery and a single significant short-distance stenosis in the proximal left anterior tibial artery. Note the slightly better image quality of CE-MRA in the distal aorta due to motion artifacts in the HR-QISS sequence. On the other hand, non-enhanced HR-QISS shows less venous overlay.</p

Contrast-enhanced (left) and non-enhanced HR-QISS (right) MRA in a 72 y/o male with PAOD stage IIb.

<p>CE-MRA and HR-QISS findings show excellent correlation. Both techniques reveal a long-distance occlusion of the right superficial femoral artery. The right superficial femoral artery is reconstituted via collaterals from the deep femoral artery. Further occlusions are found in both fibular arteries and the proximal left anterior tibial artery. High-grade stenoses are located in the right anterior tibial artery and in the left superficial femoral artery.</p