Microdialysis coupled with droplet microfluidics and mass spectrometry for determination of neurotransmitters in vivo with high temporal resolution.

Monitoring the concentration fluctuations of neurotransmitters in vivo is valuable for elucidating the chemical signals that underlie brain functions. Microdialysis sampling is a widely used tool for monitoring neurochemicals in vivo. The volume requirements of most techniques that have been coupled to microdialysis, such as HPLC, result in fraction collection times of minutes, thus limiting the temporal resolution possible. Further the time of analysis can become long for cases where many fractions are collected. Previously we have used direct analysis of dialysate by low-flow electrospray ionization-tandem mass spectrometry (ESI-MS/MS) on a triple quadrupole mass spectrometer to monitor acetylcholine, glutamate, and γ-amino-butyric acid to achieve multiplexed in vivo monitoring with temporal resolution of seconds. Here, we have expanded this approach to adenosine, dopamine, and serotonin. The method achieved limits of detection down to 2 nM, enabling basal concentrations of all these compounds, except serotonin, to be measured in vivo. Comparative analysis with LC-MS/MS showed accurate results for all compounds except for glutamate, possibly due to interference for this compound in vivo. Pairing this analysis with droplet microfluidics yields 11 s temporal resolution and can generate dialysate fractions down to 3 nL at rates up to 3 fractions per s from a microdialysis probe. The system is applied to multiplexed monitoring of neurotransmitter dynamics in response to stimulation by 100 mM K+ and amphetamine. These applications demonstrate the suitability of the droplet ESI-MS/MS method for monitoring short-term dynamics of up to six neurotransmitters simultaneously.

Improved free-breathing liver fat and iron quantification using a 2D chemical shift-encoded MRI with flip angle modulation and motion-corrected averaging.

OBJECTIVES: 3D chemical shift-encoded (CSE) MRI enables accurate and precise quantification of proton density fat fraction (PDFF) and R2*, biomarkers of hepatic fat and iron deposition. Unfortunately, 3D CSE-MRI requires reliable breath-holding. Free-breathing 2D CSE-MRI with sequential radiofrequency excitation is a motion-robust alternative but suffers from low signal-to-noise-ratio (SNR). To overcome this limitation, this work explores the combination of flip angle-modulated (FAM) 2D CSE imaging with a non-local means (NLM) motion-corrected averaging technique. METHODS: In this prospective study, 35 healthy subjects (27 children/8 adults) were imaged on a 3T MRI-system. Multi-echo 3D CSE ("3D") and 2D CSE FAM ("FAM") images were acquired during breath-hold and free-breathing, respectively, to obtain PDFF and R2* maps of the liver. Multi-repetition FAM was postprocessed with direct averaging (DA)- and NLM-based averaging and compared to 3D CSE using Bland-Altmann and regression analysis. Image qualities of PDFF and R2* maps were reviewed by two radiologists using a Likert-like scale (score 1-5, 5 = best). RESULTS: Compared to 3D CSE, multi-repetition FAM-NLM showed excellent agreement (regression slope = 1.0, R2 = 0.996) for PDFF and good agreement (regression slope 1.08-1.15, R2 ≥ 0.899) for R2*. Further, multi-repetition FAM-NLM PDFF and R2* maps had fewer artifacts (score 3.8 vs. 3.2, p < 0.0001 for PDFF; score 3.2 vs. 2.6, p < 0.001 for R2*) and better overall image quality (score 4.0 vs. 3.5, p < 0.0001 for PDFF; score 3.4 vs. 2.7, p < 0.0001 for R2*). CONCLUSIONS: Free-breathing FAM-NLM provides superior image quality of the liver compared to the conventional breath-hold 3D CSE-MRI, while minimizing bias for PDFF and R2* quantification. KEY POINTS: • 2D CSE FAM-NLM is a free-breathing method for liver fat and iron quantification and viable alternative for patients unable to hold their breath. • 2D CSE FAM-NLM is a feasible alternative to breath-hold 3D CSE methods, with low bias in proton density fat fraction (PDFF) and no clinically significant bias in R2*. • Quantitatively, multiple repetitions in 2D CSE FAM-NLM lead to improved SNR.

Effect of iodinated contrast material on post-operative eGFR when administered during renal mass ablation.

OBJECTIVE: To evaluate the effect of intravenous iodinated contrast on estimated glomerular filtration rate (eGFR) when administered immediately after thermal ablation of clinically localized T1a (cT1a) renal cell carcinoma (RCC). METHODS: This HIPAA-compliant, dual-center retrospective study was performed under a waiver of informed consent. Three hundred forty-two consecutive patients with cT1a biopsy-proven RCC were treated with percutaneous ablation between January 2010 and December 2017. Immediate post-ablation contrast-enhanced CT was the routine standard of care at one institution (contrast group), but not the other (control group). One-month pre- and 6-month post-ablation eGFR were compared using the Wilcoxon signed-rank test or the Kruskal-Wallis test. Multivariate linear regression was used to determine the effect of contrast on eGFR. A 1:1 propensity score matching was performed for all patients with a logistic model using patient, tumor, and procedural covariates. RESULTS: In total, 246 patients (158 M; median age 69 years, IQR 62-74) were included. Median tumor diameter (2.4 vs 2.5, p = 0.23) and RENAL nephrometry scores (6 vs 6, p = 0.92), surrogates for ablation zone size, were similar. Baseline kidney function was similar for the control and contrast groups, respectively (median eGFR: 70 vs 74 mL/min/1.73 m2, p = 0.29). There was an expected mild decline in eGFR after ablation (control: 70 vs 60 mL/min/1.73 m2, p < 0.001; contrast: 75 vs 71 mL/min/1.73 m2, p = 0.001). Intravenous iodinated contrast was not associated with a decline in eGFR on multivariate linear regression (1.91, 95% CI - 3.43-7.24, p = 0.46) or 1:1 propensity score-matched model (- 0.33, 95% CI - 6.81-6.15, p = 0.92). CONCLUSION: Intravenous iodinated contrast administered during ablation of cT1a RCC has no effect on eGFR. KEY POINTS: • Intravenous iodinated contrast administered during thermal ablation of clinically localized T1a renal cell carcinoma has no effect on kidney function. • Thermal ablation of clinically localized T1a renal cell carcinoma results in a mild decline in kidney function. • A decline in kidney function is similar for radiofrequency and microwave ablation of clinically localized T1a renal cell carcinoma.

Continuous and automated slug flow nanoextraction for rapid partition coefficient measurement.

Octanol-water partition coefficients (log Kow) are widely used in pharmaceutical and environmental chemistry to assess the lipophilicity of compounds. Traditionally log Kow is determined using a shake-flask method that uses milliliters of sample and solvent and requires hours for preparation, extraction, and analysis. Here, we report an automated system for rapid log Kow determination for an array of compounds using slug flow nanoextraction (SFNE) enabled by a microfluidic chip. In the method, an autosampler is used to introduce 1 µL of sample into a microfluidic device that segments the injected volume into a series of 4 nL slugs that are each paired to an adjacent octanol slug. Each octanol-water phase pair is compartmentalized by an immiscible fluorous carrier fluid. During flow, rapid extraction occurs at each octanol-water interface. The resulting linear array of slugs flows into an online UV absorbance detector that is used to determine concentrations in the phases, allowing the log Kow to be measured. The microfluidic device allows toggling between two-phase "aqueous plug" generation (aqueous sample separated by fluorous carrier fluid) and three-phase "phase pair" generation. In this way, online calibration for detection in the aqueous phase can be achieved. The method is applied to determining log Kow for a panel of seven pharmaceutical compounds, including complete calibration curves, at three different pHs in under 2 h using 5 µL of extraction standard and 2.9 µL of octanol per extraction standard analyzed.

High-Throughput Liquid-Liquid Extractions with Nanoliter Volumes.

Current methods for liquid-liquid extractions generally require microliter to milliliter volumes of solvents and sample, long equilibration times, and manual procedures. Extraction methods for samples in microfluidic systems have been limited as this tool is difficult to implement on the nanoliter or smaller scale. We have developed slug-flow nanoextraction (SFNE), a method based on droplet microfluidics that allows multiple liquid-liquid extractions to be performed simultaneously in a capillary tube, using only 5 nL of sample and extraction solvent per extraction. Each two-phase slug is segmented from the others by immiscible carrier fluid. We found rapid extractions (<5 s), partition coefficients matching those achieved at larger scale extractions, and potential to preconcentrate samples through volume manipulation. This method was used to accurately and rapidly determine octanol-water partition coefficients (Kow), determining identical Kow as the shake-flask method for acetaminophen, Kow = 2.48 ± 0.02. The measurement, along with calibration and 12 replicates, was complete within 5 min, consuming under 150 nL of solvent and sample. The method was also applied to extract analytes from complex biological samples prior to electrospray ionization-tandem mass spectrometry (ESI-MS/MS) at a rate of 6 s per sample, allowing for simultaneous determination of five different drugs spiked into human plasma, synthetic urine (SU), and artificial cerebral spinal fluid (aCSF) using ethyl acetate as the extraction phase. The signal-to-noise (S/N) for analytes improved up to 19-fold compared to direct ESI-MS of single-phase droplets (aqueous plugs segmented by carrier fluid), with limits of detection down to 7 nM (35 amol).

Pharmacokinetics of Ferumoxytol in the Abdomen and Pelvis: A Dosing Study with 1.5- and 3.0-T MRI Relaxometry.

Background The off-label use of ferumoxytol (FE), an intravenous iron preparation for iron deficiency anemia, as a contrast agent for MRI is increasing; therefore, it is critical to understand its pharmacokinetics. Purpose To evaluate the pharmacokinetics of FE in the abdomen and pelvis, as assessed with quantitative 1.5- and 3.0-T MRI relaxometry. Materials and Methods R2*, an MRI technique used to estimate tissue iron content in the abdomen and pelvis, was performed at 1.5 and 3.0 T in 12 healthy volunteers between April 2015 and January 2016. Volunteers were randomly assigned to receive an FE dose of 2 mg per kilogram of body weight (FE2mg) or 4 mg/kg (FE4mg). MRI was repeated at 1.5 and 3.0 T for each volunteer at five time points: days 1, 2, 4, 7, and 30. A radiologist experienced in MRI relaxometry measured R2* in organs of the mononuclear phagocyte system (MPS) (ie, liver, spleen, and bone marrow), non-MPS anatomy (kidney, pancreas, and muscle), inguinal lymph nodes (LNs), and blood pool. A paired Student t test was used to compare changes in tissue R2*. Results Volunteers (six female; mean age, 44.3 years ± 12.2 [standard deviation]) received either FE2 mg (n = 5) or FE4 mg (n = 6). Overall R2* trend analysis was temporally significant (P < .001). Time to peak R2* in the MPS occurred on day 1 for FE2mg and between days 1 and 4 for FE4mg (P < .001 to P < .002). Time to peak R2* in non-MPS anatomy, LNs, and blood pool occurred on day 1 for both doses (P < .001 to P < .09). Except for the spleen (at 1.5 T) and liver, MPS R2* remained elevated through day 30 for both doses (P = .02 to P = .03). Except for the kidney and pancreas, non-MPS, LN, and blood pool R2* returned to baseline levels between days 2 and 4 at FE2mg (P = .06 to P = .49) and between days 4 and 7 at FE4mg (P = .06 to P = .63). There was no difference in R2* change between non-MPS and LN R2* at any time (range, 1-71 sec-1 vs 0-50 sec-1; P = .06 to P = .97). Conclusion The pharmacokinetics of ferumoxytol in lymph nodes are distinct from those in mononuclear phagocyte system (MPS) organs, parallel non-MPS anatomy, and the blood pool. © RSNA, 2019 Online supplemental material is available for this article.

Stimulated-echo diffusion-weighted imaging with moderate b values for the detection of prostate cancer.

OBJECTIVES: Conventional spin-echo (SE) DWI leads to a fundamental trade-off depending on the b value: high b value provides better lesion contrast-to-noise ratio (CNR) by sacrificing signal-to-noise ratio (SNR), image quality, and quantitative reliability. A stimulated-echo (STE) DWI acquisition is evaluated for high-CNR imaging of prostate cancer while maintaining SNR and reliable apparent diffusion coefficient (ADC) mapping. METHODS: In this prospective, IRB-approved study, 27 patients with suspected prostate cancer (PCa) were scanned with three DWI sequences (SE b = 800 s/mm2, SE b = 1500 s/mm2, and STE b = 800 s/mm2) after informed consent was obtained. ROIs were drawn on biopsy-confirmed cancer and non-cancerous tissue to perform quantitative SNR, CNR, and ADC measurements. Qualitative metrics (SNR, CNR, and overall image quality) were evaluated by three experienced radiologists. Metrics were compared pairwise between the three acquisitions using a t test (quantitative metrics) and Wilcoxon rank test (qualitative metrics). RESULTS: Quantitative measurements showed that STE DWI at b = 800 s/mm2 has significantly better SNR compared to SE DWI at b = 1500 s/mm2 (p < 0.0001) and comparable CNR to high-b value SE DWI at b = 1500 s/mm2 (p < 0.05) in the peripheral zone. Qualitative assessment showed preference to STE b = 800 s/mm2 in SNR and SE b = 1500 s/mm2 in CNR. The overall image quality and lesion detectability among most readers showed no significant preference between STE b = 800 s/mm2 and SE b = 1500 s/mm2. Further, STE DWI had similar ADC contrast between lesion and normal tissue as SE DWI at b = 800 s/mm2 (p = 0.90). CONCLUSION: STE DWI has the potential to provide high-SNR, high-CNR imaging of prostate cancer while also enabling reliable ADC mapping. KEY POINTS: • Quantitative analysis showed that STE DWI at b = 800 s/mm2is able to achieve simultaneously high CNR, high SNR, and reliable ADC mapping, compared to SE b = 800 s/mm2and SE b = 1500 s/mm2. • Qualitative assessment by three readers showed that STE DWI at b = 800 s/mm2has significantly higher SNR than SE b = 1500 s/mm2. No preference between SE b = 1500 s/mm2and STE b = 800 s/mm2was determined in terms of CNR with no missed lesions were found in both acquisitions. • A single STE DWI acquisition at moderate b value (800-1000 s/mm2) may provide sufficient image quality and quantitative reliability for prostate cancer imaging within a shorter scan time, in place of two DWI acquisitions (one with moderate b value and one with high b value).

Bosniak Classification of Cystic Renal Masses, Version 2019: An Update Proposal and Needs Assessment.

Cystic renal cell carcinoma (RCC) is almost certainly overdiagnosed and overtreated. Efforts to diagnose and treat RCC at a curable stage result in many benign neoplasms and indolent cancers being resected without clear benefit. This is especially true for cystic masses, which compared with solid masses are more likely to be benign and, when malignant, less aggressive. For more than 30 years, the Bosniak classification has been used to stratify the risk of malignancy in cystic renal masses. Although it is widely used and still effective, the classification does not formally incorporate masses identified at MRI or US or masses that are incompletely characterized but are highly likely to be benign, and it is affected by interreader variability and variable reported malignancy rates. The Bosniak classification system cannot fully differentiate aggressive from indolent cancers and results in many benign masses being resected. This proposed update to the Bosniak classification addresses some of these shortcomings. The primary modifications incorporate MRI, establish definitions for previously vague imaging terms, and enable a greater proportion of masses to enter lower-risk classes. Although the update will require validation, it aims to expand the number of cystic masses to which the Bosniak classification can be applied while improving its precision and accuracy for the likelihood of cancer in each class.

Stimulated echo based mapping (STEM) of T1 , T2 , and apparent diffusion coefficient: validation and protocol optimization.

PURPOSE: To present a stimulated-echo based mapping (STEM) approach for simultaneous T1 , T2 , and ADC mapping. METHODS: Diffusion-weighted stimulated-echo images with various combinations of mixing time (TM), TE, and b-value were acquired to enable simultaneous mapping of T1 , T2 , and ADC. The proposed STEM method was performed by densely sampling the TM-TE-b space in a phantom and in brain and prostate of healthy volunteers. T1 , T2 , and ADC from STEM were compared to reference mapping methods. Additionally, protocol optimization was performed to enable rapid STEM acquisition within 2 min by sparsely sampling the TM-TE-b space. The T1 , T2 , and ADC measurements from rapid acquisitions were compared to the densely sampled STEM for evaluation. Finally, a patient with biopsy-proven high-risk prostate cancer was imaged to demonstrate the ability of STEM to differentiate cancer and healthy tissues. RESULTS: Relative to the reference measurements, densely sampled STEM provided accurate quantitative T1 , T2 , and ADC mapping in phantoms (R2 = 0.999, slope between 0.97-1.03), as well as in brain and prostate. Further, the T1 , T2 , and ADC measurements from the optimized rapid STEM acquisitions agreed closely with densely sampled STEM. Finally, STEM showed decreased T2 and ADC in prostate cancer compared to healthy prostate tissue. CONCLUSION: STEM provides accurate simultaneous mapping of T1 , T2 , and ADC. This method may enable rapid and accurate multi-parametric tissue characterization for clinical and research applications.

Risk Factors for Complications and Nondiagnostic Results following 1,155 Consecutive Percutaneous Core Renal Mass Biopsies.

PURPOSE: The purpose of this study was to evaluate patient, tumor and technical factors associated with procedural complications and nondiagnostic findings following percutaneous core renal mass biopsy. MATERIALS AND METHODS: We reviewed core renal mass biopsies from 2000 to 2017. Complications at 30 days or less were graded using the Clavien-Dindo system. Univariate and multivariable analyses were done to evaluate associations between clinical characteristics and the risk of complications or nondiagnostic findings. RESULTS: Of the 1,155 biopsies performed in a total of 965 patients procedural complications were identified in 24 patients (2.2%), including 5 (0.4%) with major complications (Clavien 3a or greater). No patients were identified with tumor seeding of the biopsy tract. Patient age, body mass index, gender, Charlson comorbidity index, smoking, mass diameter, nephrometry score, number of cores and prior biopsy were not associated with complication risk (p = 0.06 to 0.53). Complications were not increased for patients on aspirin or those with low platelets (25,000 to 160,000/µl blood) or a mildly elevated INR (international normalized ratio) (1.2 to 2.0, p = 0.16, 0.07 and 0.50, respectively). The complication risk was not increased during the initial 50 cases of a radiologist or when a trainee was present (p = 0.35 and 0.12, respectively). Nondiagnostic findings were present in 14.6% of biopsies. Independent predictors included cystic features, contrast enhancement, mass diameter and skin-to-mass distance (p <0.001, 0.002, 0.02 and 0.049, respectively). Radiologist experience was not associated with the nondiagnostic rate (p = 0.23). Prior nondiagnostic biopsy was not associated with an increased nondiagnostic rate on subsequent attempts (19.2% vs 14.2%, p = 0.23). CONCLUSIONS: Procedural complications following biopsy are rare even with low serum platelets, a mildly elevated INR or when the patient remains on aspirin. Cystic features, hypo-enhancement on imaging, a smaller mass diameter and a longer skin-to-tumor distance increase the risk of nondiagnostic findings.

CE-MS with electrokinetic supercharging and application to determination of neurotransmitters.

Electrokinetic supercharging (EKS) is known as one of the most effective online electrophoretic preconcentration techniques, though pairing with it with mass spectrometry has presented challenges. Here, EKS is successfully paired with ESI-MS/MS to provide a sensitive and robust method for analysis of biogenic amines in biological samples. Injection parameters including electric field strength and the buffer compositions used for the separation and focusing were investigated to achieve suitable resolution, high sensitivity, and compatibility with ESI-MS. Using EKS, the sensitivity of the method was improved 5000-fold compared to a conventional hydrodynamic injection with CZE. The separation allowed for baseline resolution of several neurotransmitters within 16 min with LODs down to 10 pM. This method was applied to targeted analysis of seven biogenic amines from rat brain stem and whole Drosophila tissue. This is the first method to use EKS with CE-ESI-MS/MS to analyze biological samples.

Tumor location does not impact oncologic outcomes for percutaneous microwave ablation of clinical T1a renal cell carcinoma.

OBJECTIVE: To evaluate the impact of anterior tumor location on oncologic efficacy, complication rates, and procedure duration for 151 consecutive biopsy-proven clinical T1a renal cell carcinoma (RCC) treated with percutaneous microwave (MW) ablation. METHODS: This single-center retrospective study was performed under a waiver of informed consent. One hundred forty-eight consecutive patients (103 M/45 F; median age 67 years, IQR 61-73) with 151 cT1a biopsy-proven RCC (median diameter 2.4 cm, IQR 1.9-3.0) were treated with percutaneous MW ablation between March 2011 and August 2017. Patient and procedural data collected included Charlson comorbidity index (CCI), RENAL nephrometry score (NS), use of hydrodisplacement, MW antennas/generator output/time, and procedure time (PT). Data were stratified by anterior, posterior, and midline tumor location and compared with the Kruskal-Wallis or chi-squared tests. The Kaplan-Meier method was used for survival analyses. RESULTS: Tumor size, NS, and use/volume of hydrodisplacement were similar for posterior and anterior tumors (p > 0.05). Patients with anterior tumors had a higher CCI (3 vs 4, p = 0.001). Median PT for posterior and anterior tumors was similar (100 vs 108 min, p = 0.26). Single session technical success and primary efficacy were achieved for all 151 tumors including 61 posterior and 67 anterior tumors. The 4 (3%) Clavien III-IV complications and 6 (4%) local recurrences were not associated with tumor location (p > 0.05). Three-year RFS, CSS, and OS were 95% (95% CI 0.87, 0.98), 100% (95% CI 1.0, 1.0), and 96% (95% CI 0.89, 0.98), respectively. CONCLUSIONS: The safety and efficacy of percutaneous microwave ablation for anterior and posterior RCC are similar. KEY POINTS: • The safety profile for percutaneous microwave ablation of anterior and posterior T1a renal cell carcinoma is equivalent. • Percutaneous microwave ablation of T1a renal cell carcinoma provides durable oncologic control regardless of tumor location. • Placement of additional microwave antennas and use of hydrodisplacement are associated with longer procedure times.

Percutaneous Microwave Tumor Ablation Is Safe in Patients with Cardiovascular Implantable Electronic Devices: A Single-Institutional Retrospective Review.

The risk of electromagnetic interference between microwave (MW) ablation and cardiac implantable electronic devices (CIEDs), ie, pacemakers and defibrillators, has not been fully evaluated. Fourteen MW ablations (kidney, n = 8; liver, n = 5; lung, n = 1) were performed in 13 patients with CIEDs in normal operating mode. Electrocardiography tracings, cardiovascular complications, tumor size, tumor-to-CIED distance, and tumor-to-device lead distance were recorded. Mean tumor size was 2.9 cm, mean tumor-to-CIED distance was 26.4 cm (range, 9-30 cm), and mean tumor-to-lead distance was 12.1 cm (range, 3.5-20 cm). No device-based cardiovascular complications or class C or higher complications per Society of Interventional Radiology criteria were identified. MW ablation appears to be safe in select patients with CIEDs.

Effect of Tumor Complexity and Technique on Efficacy and Complications after Percutaneous Microwave Ablation of Stage T1a Renal Cell Carcinoma: A Single-Center, Retrospective Study.

Purpose To evaluate the effects of tumor complexity and technique on early and midterm oncologic efficacy and rate of complications for 100 consecutive biopsy-proved stage T1a renal cell carcinomas (RCCs) treated with percutaneous microwave ablation. Materials and Methods This HIPAA-compliant, single-center retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety-six consecutive patients (68 men, 28 women; mean age, 66 years ± 9.4) with 100 stage T1a N0M0 biopsy-proved RCCs (median diameter, 2.6 cm ± 0.8) underwent percutaneous microwave ablation between March 2011 and June 2015. Patient and procedural data were collected, including body mass index, comorbidities, tumor histologic characteristics and grade, RENAL nephrometry score, number of antennas, generator power, and duration of ablation. Technical success, local tumor progression, and presence of complications were assessed at immediate and follow-up imaging. The Kaplan-Meier method was used for survival analyses. Results Technical success was achieved for all 100 tumors (100%), including 47 moderately and five highly complex RCCs. Median clinical and imaging follow-up was 17 months (range, 0-48 months) and 15 months (range, 0-44 months), respectively. No change in estimated glomerular filtration rate was noted after the procedure (P = .49). There were three (3%) procedure-related complications and six (6%) delayed complications, all urinomas. One case of local tumor progression (1%) was identified 25 months after the procedure. Three-year local progression-free survival, cancer-specific survival, and overall survival were 88% (95% confidence interval: 0.52%, 0.97%), 100% (95% confidence interval: 1.0%, 1.0%), and 91% (95% confidence interval: 0.51%, 0.99%), respectively. Conclusion Percutaneous microwave ablation is an effective and safe treatment option for stage T1a RCC, regardless of tumor complexity. Long-term follow-up is needed to establish durable oncologic efficacy and survival relative to competing ablation modalities and surgery. © RSNA, 2017.

Crossover comparison of ferumoxytol and gadobenate dimeglumine for abdominal MR-angiography at 3.0 tesla: Effects of contrast bolus length and flip angle.

PURPOSE: Ferumoxytol (FE) has gained interest as an alternative to gadolinium-based contrast agents (GBCAs). The purpose of this study was to evaluate and optimize ferumoxytol dose and T1 weighting, in comparison to a conventional GBCA. MATERIALS AND METHODS: Twelve healthy volunteers (six women / six men, mean age 44.3 years) were recruited for this study. Scanning was performed on a clinical 3 Tesla (T) MRI system. Gadobenate dimeglumine (GD)-enhanced MRA was performed followed by FE-enhanced MRA 1 month later. Volunteers were randomly assigned to a diluted (n = 6) or undiluted (n = 6) dose of GD (0.1 mmol/kg), and to FE doses of 4 mg/kg (n = 6) or 2 mg/kg (n = 6). First pass and steady-state MRA were performed for GD- and FE-enhanced MRA. Flip-angle optimization was performed after FE administration. Quantitative analysis included relative contrast-to-noise ratio (relCNR) measurements for all acquisitions. First pass GD- and FE-enhanced MRA images were evaluated qualitatively. RESULTS: RelCNR was significantly higher with undiluted GD (31.8, 95% confidence interval [CI], 27.7-35.9) compared with diluted GD (16.2; 95% CI, 12.2-20.3; P = 0.001) and both 4 mg/kg FE (12.5; 95% CI, 8.5-16.4; P < 0.001) and 2 mg/kg FE (9.1; 95% CI, 5.1-13.2; P < 0.001) during first pass. Relative CNR did not decrease with FE 5 min postinjection compared with GD. Flip-angle analysis revealed relative CNR-peaks at 30° for FE 4 mg/kg and at 20° for FE 2 mg/kg. Diluted GD (P = 0.013) and FE 4 mg/kg (P = 0.01) revealed significantly higher image quality scores compared with undiluted GD during first pass. CONCLUSION: This study shows an equivalent image quality of FE and GD for first pass MRA even though GD showed significantly higher relative CNR. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1617-1626.

Safety and Efficacy of Percutaneous Microwave Hepatic Ablation Near the Heart.

PURPOSE: To evaluate safety and efficacy of percutaneous hepatic microwave (MW) ablation performed near the heart. MATERIALS AND METHODS: This study reviewed 118 consecutive peripheral (ablation zone margins within 5 mm of liver capsule) percutaneous MW hepatic ablations performed between June 2010 and August 2015. Ablation zones of 27 tumors (22.8%) extended to ≤ 5 mm from myocardium, and these ablations comprised the study group; the remaining ablations formed the control group. The study cohort included 14 men and 10 women (mean age, 59 y) with 16 hepatocellular carcinomas, 9 metastases, and 2 hemangiomas. Periprocedural imaging was used to evaluate tumor size and distance from the heart, ablation zone size, and complications. Mean tumor size and distance to myocardium were 2.6 cm ± 1.7 and 1.1 cm ± 1.1, respectively. The electronic medical record was used to retrospectively assess local tumor progression (LTP) and electrocardiogram and hemodynamic alterations during and after ablation. Statistical analysis was performed with Fisher exact test and t test. RESULTS: Median follow-up was 13.6 months (range, 1.2-38.7 months). No arrhythmias occurred during or after ablation in the follow-up period (0/27). There was no difference between groups in frequency of alterations in periprocedural blood pressure (25.9% vs 29.6%, p=0.81) or heart rate (18.5% vs 24.2%, P = .61) or rate of LTP (12.0% vs 10.8%, P = 1.0). CONCLUSIONS: Percutaneous MW ablation near the heart may be safe and effective, without increased risk of cardiac complications and with similar rates of LTP, compared with a control group of peripheral liver ablations.

Metal cation control of electroosmotic flow magnitude in phospholipid-coated capillaries.

CZE has become widespread for the separation and analysis of biomolecules such as proteins and peptides, due to factors such as, the speed of the separations, low sample volume, and high resolution associated with the technique. However, the separation of biomolecules by CZE does present a significant challenge due to the electrostatic attraction and adsorption of cationic, or cation containing, biomolecules to the capillary surface. To that end numerous methods have been developed to passivate, or protect the surface, in order to prevent the adsorption of analytes. Yet, in the process of protecting the capillary surface, the potential for further modification of the EOF, a factor crucial to effective analyte resolution, is greatly diminished. In seeking to overcome this limitation we have explored the potential of incorporating a range of metal cations into a phospholipid bilayer capillary coating. It has previously been established that the inclusion of calcium into the separation buffer with a phospholipid coating will reverse the EOF in the capillary. Here, we present our investigation of a broader range of metal cations included in the separation buffer (Ca(2+) , Mg(2+) , Co(2+) , Ni(2+) , Sr(2+) , Ba(2+) , and Ce(3+) ) revealing that the choice of metal cation can drastically influence the EOF, with observed values between -3.80 × 10(-4) and -5.74 × 10(-5) cm(2) /V·s.

Microwave versus Radiofrequency Ablation Treatment for Hepatocellular Carcinoma: A Comparison of Efficacy at a Single Center.

PURPOSE: To compare efficacy and major complication rates of radiofrequency (RF) and microwave (MW) ablation for treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective single-center study included 69 tumors in 55 patients treated by RF ablation and 136 tumors in 99 patients treated by MW ablation between 2001 and 2013. RF and MW ablation devices included straight 17-gauge applicators. Overall survival and rates of local tumor progression (LTP) were evaluated using Kaplan-Meier techniques with Cox proportional hazard ratio (HR) models and competing risk regression of LTP. RESULTS: RF and MW cohorts were similar in age (P = .22), Model for End-Stage Liver Disease score (P = .24), and tumor size (mean 2.4 cm [range, 0.6-4.5 cm] and 2.2 cm [0.5-4.2 cm], P = .09). Median length of follow-up was 31 months for RF and 24 months for MW. Rate of LTP was 17.7% with RF and 8.8% with MW. Corresponding HR from Cox and competing risk models was 2.17 (95% confidence interval [CI], 1.04-4.50; P = 0.04) and 2.01 (95% CI, 0.95-4.26; P = .07), respectively. There was improved survival for patients treated with MW ablation, although this was not statistically significant (Cox HR, 1.59 [95% CI, 0.91-2.77; P = .103]). There were few major (≥ grade C) complications (2 for RF, 1 for MW; P = .28). CONCLUSIONS: Treating HCC percutaneously with RF or MW ablation was associated with high primary efficacy and durable response, with lower rates of LTP after MW ablation.

Technical feasibility of uro-dynamic MRI study of voiding biomechanics: a pilot study.

INTRODUCTION: Dynamic volumetric MRI was used to non-invasively assess voiding biomechanics in a healthy male volunteer. METHODS: Using 3D Differential Subsampling with Cartesian Ordering (DISCO) Flex acquisition sequence, volumetric bladder images were obtained throughout the voiding effort. These were subsequently segmented using MIMICS. Segmented anatomical volumes were used to quantify total voided volume, post-void residual, volumetric displacement of urine over time, bladder neck angle, sphericity index, and prostatic urethral angle through the voiding effort. RESULTS: Bladder sphericity index correlated positively with flow rate. The greatest degree of bladder neck funneling correlated with the maximum urine flow rate. There was straightening of the prostatic urethral angle during voiding that also correlated positively with urine flow. CONCLUSION: This pilot study confirms the potential of dynamic MRI to provide non-invasive assessment of lower urinary tract anatomy and biomechanics during voiding.

Imaging Genomics and Multiomics: A Guide for Beginners Starting Radiomics-Based Research.

Radiomics uses advanced mathematical analysis of pixel-level information from radiologic images to extract existing information in traditional imaging algorithms. It is intended to find imaging biomarkers related to the genomics of tumors or disease patterns that improve medical care by advanced detection of tumor response patterns in tumors and to assess prognosis. Radiomics expands the paradigm of medical imaging to help with diagnosis, management of diseases and prognostication, leveraging image features by extracting information that can be used as imaging biomarkers to predict prognosis and response to treatment. Radiogenomics is an emerging area in radiomics that investigates the association between imaging characteristics and gene expression profiles. There are an increasing number of research publications using different radiomics approaches without a clear consensus on which method works best. We aim to describe the workflow of radiomics along with a guide of what to expect when starting a radiomics-based research project.