A radiomic biomarker for prognosis of resected colorectal cancer liver metastases generalizes across MRI contrast agents.

Introduction: Contrast-enhanced MRI is routinely performed as part of preoperative work-up for patients with Colorectal Cancer Liver Metastases (CRLM). Radiomic biomarkers depicting the characteristics of CRLMs in MRI have been associated with overall survival (OS) of patients, but the reproducibility and clinical applicability of these biomarkers are limited due to the variations in MRI protocols between hospitals. Methods: In this work, we propose a generalizable radiomic model for predicting OS of CRLM patients who received preoperative chemotherapy and delayed-phase contrast enhanced (DPCE) MRIs prior to hepatic resection. This retrospective two-center study included three DPCE MRI cohorts (n=221) collected between January 2006 and December 2012. A 10-minute delayed Gd-DO3A-butrol enhanced MRI discovery cohort was used to select features based on robustness across contrast agents, correlation with OS and pairwise Pearson correlation, and to train a logistic regression model that predicts 3-year OS. Results: The model was evaluated on a 10-minute delayed Gd-DO3A-butrol enhanced MRI validation cohort (n=121), a 20-minute delayed Gd-EOB-DTPA (n=72) cohort from the same institute, and a 5-minute delayed Gd-DTPA cohort (n=28) from an independent institute. Two features were selected: minor axis length and dependence variance. The radiomic signature model stratified high-risk and low-risk CRLM groups in the Gd-DO3Abutrol (HR = 6.29, p = .007), Gd-EOB-DTPA (HR = 3.54, p = .003) and Gd-DTPA (HR = 3.16, p = .04) validation cohorts. Discussion: While most existing MRI findings focus on a specific contrast agent, our study shows the potential of MRI features to be generalizable across main-stream contrast agents at delayed phase.

Variables Influencing Radiology Volume Recovery During the Next Phase of the Coronavirus Disease 2019 (COVID-19) Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has reduced radiology volumes across the country as providers have decreased elective care to minimize the spread of infection and free up health care delivery system capacity. After the stay-at-home order was issued in our county, imaging volumes at our institution decreased to approximately 46% of baseline volumes, similar to the experience of other radiology practices. Given the substantial differences in severity and timing of the disease in different geographic regions, estimating resumption of radiology volumes will be one of the next major challenges for radiology practices. We hypothesize that there are six major variables that will likely predict radiology volumes: (1) severity of disease in the local region, including potential subsequent "waves" of infection; (2) lifting of government social distancing restrictions; (3) patient concern regarding risk of leaving home and entering imaging facilities; (4) management of pent-up demand for imaging delayed during the acute phase of the pandemic, including institutional capacity; (5) impact of the economic downturn on health insurance and ability to pay for imaging; and (6) radiology practice profile reflecting amount of elective imaging performed, including type of patients seen by the radiology practice such as emergency, inpatient, outpatient mix and subspecialty types. We encourage radiology practice leaders to use these and other relevant variables to plan for the coming weeks and to work collaboratively with local health system and governmental leaders to help ensure that needed patient care is restored as quickly as the environment will safely permit.

Late Gadolinium Hyperintensity of Suspected Colorectal Liver Metastases on Gadofosveset-Enhanced Magnetic Resonance Imaging: A Predictor of Benignity and a Potential Problem-Solving Tool.

PURPOSE: Late gadolinium hyperintensity (LGH) is sometimes seen in colorectal liver metastasis (CRLM) and represents a significant diagnostic pitfall due to overlap with LGH in benign hemangiomas; therefore, the objective of this study was to determine the prevalence of LGH and the ability of LGH to differentiate between CRLM and benign lesions with intravascular (gadofosveset) vs extracellular contrast agents (gadobutrol). METHODS: Patients with known colorectal cancer and suspected liver lesions were prospectively recruited into this institutional review board-approved, single institution study and received magnetic resonance imaging of the liver with gadofosveset and gadobutrol. The prevalence of LGH for CRLMs and solid benign lesions was determined. Receiver operating characteristics curves were determined for the presence of LGH as a predictor of benignity. The utility of LGH to differentiate between CRLM and solid benign lesions using gadofosveset vs gadobutrol was compared using the generalized estimating equation. RESULTS: Twenty-five patients with 131 solid focal liver lesions were recruited. The prevalence of LGH of CRLMs was 11.2% (95% confidence interval [CI]: 0.5%-21.8%) with gadofosveset vs 63.7% (95% CI: 45.7%-81.7%) with gadobutrol. The area under the receiver operating characteristic curve for the presence of LGH as a predictor of benignity was 0.86 using gadofosveset vs 0.75 using gadobutrol. Both LGH (P = .003) and the interaction of contrast agent and LGH (P = .003) statistically significantly differentiated CRLM from benign lesions. CONCLUSION: LGH is more common with extracellular than with intravascular contrast agents and is statistically significantly associated with benign lesions rather than metastases.

Tumor enhancement of colorectal liver metastases on preoperative gadobutrol-enhanced MRI at 5 minutes post-contrast injection is associated with overall survival post-hepatectomy.

Previous studies have demonstrated that target tumor enhancement (TTE) of colorectal cancer liver metastases (CRCLM) on 10-minute delayed phase gadobutrol-enhanced MRI is associated with overall survival post-hepatectomy. The purpose of this study was to determine whether TTE of CRCLM on preoperative gadobutrol-enhanced MRI measured at 5-minute delayed phase is also associated with overall survival. We performed a single-institution, REB-approved, retrospective study of 121 patients with CRCLM who had received a clinical gadobutrol-enhanced MRI after treatment with chemotherapy and prior to liver surgery between January 1, 2006 and December 31, 2012. The TTE of the colorectal liver metastases (CRLM) on 5-minute delayed phase was determined. Kaplan-Meier and Cox-regression survival analyses were used in order to determine the association between TTE on 5-minute delayed phase and overall survival, after adjusting for known prognostic variables. TTE of chemotherapy-treated CRLM on gadobutrol-enhanced MRI at 5-minute post-contrast injection is associated with overall survival post-hepatectomy. On Kaplan-Meier survival analysis, there was a significant difference in overall survival between strong and weak TTE groups (log-rank P=0.009) with 74.4% survival at 36 months in the strong TTE group compared to only 44.6% in the weak TTE group. On Cox-regression analysis, the adjusted hazard ratio of death for patients with low TTE was 0.40 (95% CI: 0.18-0.90, P=0.026), after adjusting for known prognostic variables. This study provides preliminary evidence that tumor enhancement of CRLM at 5 minutes post-contrast injection on gadobutrol-enhanced MRI may provide preoperative prognostic information. This may be helpful for risk stratification of patients for surgery.

Late gadolinium MRI enhancement of colorectal liver metastases is associated with overall survival among nonsurgical patients.

PURPOSE: To determine if late gadolinium MRI enhancement of colorectal liver metastases (CRCLM) is associated with overall survival among nonsurgical patients. MATERIALS AND METHODS: This retrospective study was approved by the institutional research ethics board. Late gadolinium enhancement was measured using target tumour enhancement (TTE) in all nonsurgical patients with CRCLM who received a 10-min delayed phase gadobutrol-enhanced liver MRI between March 1, 2006, and August 31, 2014. A total of 122 patients met inclusion/exclusion criteria. Patients were dichotomized into strong and weak TTE. Kaplan-Meier and Cox regression statistics were used to determine whether TTE was associated with overall survival. Noncontributory potential confounding variables (age, sex, number and size of metastases, carcinoembryonic (CEA) level, and presence of extrahepatic disease) were excluded from the final Cox regression model using the backward Wald elimination. Subgroup Kaplan-Meier survival analyses were performed on patients who were chemotherapy-naïve and chemotherapy-treated at the time of MRI. RESULTS: Strong TTE had increased survival compared with those with weak TTE on Kaplan-Meier analysis (2-year survival: 69.8% vs. 43.5%, p = 0.002). Among 96 patients where data was available for multivariable analysis, weak TTE was associated with death (adjusted hazard ratio 0.25, 95% CI 0.11-0.59, p = 0.002), after adjusting for CEA level. Other potential confounders were noncontributory. Subgroup analyses demonstrated that strong TTE had increased survival compared with those with weak TTE in both the chemotherapy-naïve (p = 0.047) and chemotherapy-treated (p = 0.008) groups. CONCLUSION: Strong late gadolinium MRI enhancement of CRCLM is associated with overall survival among nonsurgical patients. KEY POINTS: • MRI enhancement of colorectal liver metastases is associated with overall survival in nonsurgical patients. • MRI enhancement of colorectal liver metastases is associated with overall survival in both chemotherapy-naïve and chemotherapy-treated subgroups.

Delayed tumour enhancement on gadoxetate-enhanced MRI is associated with overall survival in patients with colorectal liver metastases.

OBJECTIVES: To determine whether tumour enhancement on preoperative delayed-phase gadoxetate-enhanced MRI can predict long-term survival in patients with colorectal liver metastases (CRCLM) post-hepatectomy. MATERIALS AND METHODS: Sixty-five patients who received a preoperative gadoxetate-enhanced MRI prior to liver resection for CRCLM from January 1, 2010, to December 31, 2012, were included in this retrospective study. Target tumour enhancement (TuEn) was calculated as the mean percentage increase in SNR from precontrast to 10-min or 20-min delayed phase for up to two target lesions. Per-patient TuEn was stratified into weak and strong enhancement based on the cut-off determined by the Youden Index for 3-year survival. Kaplan-Meier and Cox regression analyses were used to determine whether tumour enhancement could predict overall survival independent of potential confounders (clinical risk score). RESULTS: The proportion surviving at 3 years was 85.1% in patients with strong TuEn at 10 min vs. 56.5% in those with weak TuEn at 10 min (p = 0.001). The proportion surviving at 3 years was 79.4% in patients with strong TuEn at 20 min vs. 58.7% in those with weak TuEn at 20 min (p = 0.011). After adjusting for potential confounders, the hazard ratio of death was 0.24 (p = 0.009) in patients who had weak TuEn at 10 min and 0.32 (p = 0.018) in patients who had weak TuEn at 20 min. CONCLUSIONS: Strong delayed tumour enhancement seen on gadoxetate-enhanced MRI is associated with overall survival in patients with CRCLM post-hepatectomy and may be useful for preoperative risk stratification. KEY POINTS: • Delayed tumour enhancement of colorectal liver metastases on gadoxetate-enhanced MRI is associated with survival post-hepatectomy • Delayed tumour enhancement of colorectal liver metastases on gadoxetate-enhanced MRI can be measured at both 10 min and 20 min post-contrast injection.

Late gadolinium enhancement of colorectal liver metastases post-chemotherapy is associated with tumour fibrosis and overall survival post-hepatectomy.

PURPOSE: To determine whether late gadolinium MRI enhancement of colorectal liver metastases (CRCLM) post-chemotherapy is associated with tumour fibrosis and survival post-hepatectomy. MATERIALS AND METHODS: The institutional review board approved this retrospective cohort study and waived the requirement for informed consent. A cohort of 121 surgical patients who received preoperative MRI after chemotherapy between 2006-2012 was included in this study. Target tumour enhancement (TTE), defined as the mean contrast-to-noise ratio of up to two target lesions on late-phase gadobutrol-enhanced MRI, was determined by two independent raters. The average TTE was correlated with tumour fibrosis on post-hepatectomy specimens using Spearman correlation and with survival post-hepatectomy using Kaplan-Meier and Cox regression. Inter-rater reliability was determined using relative intra-class correlation coefficients. RESULTS: In the surgical cohort (mean age: 63.0 years; male: 58%), TTE was associated with tumour fibrosis (r = 0.43, p < 0.001). Strong TTE was associated with improved survival compared to weak TTE (3-year survival: 88.4% vs. 58.8%, p = 0.003) with a hazard ratio of 0.32 (95% CI: 0.14-0.75, p = 0.008), after taking into account known prognostic variables. Inter-rater reliability was very good with a relative intraclass correlation of 0.84 (95% CI: 0.77-0.89). CONCLUSION: Late gadolinium MRI enhancement of CRCLM post-chemotherapy is associated with tumour fibrosis and survival. KEY POINTS: • MRI enhancement of colorectal liver metastases is associated with survival post-hepatectomy • MRI enhancement of chemotherapy-treated colorectal liver metastases correlates with tumour fibrosis • Measuring late MRI enhancement using target tumour enhancement is reliable.

Late stage complicated atheroma in low-grade stenotic carotid disease: MR imaging depiction--prevalence and risk factors.

PURPOSE: To determine if complicated plaque can be found by using magnetic resonance (MR) imaging-depicted intraplaque hemorrhage (IPH), even among symptomatic patients with low-grade (≤50%) carotid stenosis. MATERIALS AND METHODS: The institutional ethics review board approved this retrospective study and waived requirements for written informed consent. Symptomatic patients with bilateral 0%-50% carotid stenosis referred for carotid MR imaging were considered. Risk factors (age, sex, hypertension, diabetes, hyperlipidemia, myocardial infarction, atrial fibrillation, smoking, coronary artery disease, and cerebrovascular disease), medications (antihypertensive drugs, diabetes drugs, statins, and aspirin), and the brain side causing symptoms were recorded. MR-depicted IPH prevalence in the carotid arteries ipsilateral and contralateral to the symptomatic side was compared by using the Fisher exact test. Multivariable regression was used to compare the MR-depicted IPH prevalence, while adjusting for risk factors and medications. RESULTS: A total of 217 patients (434 carotid arteries) were included. MR-depicted IPH was found in 13% (31 of 233) of carotid arteries ipsilateral and 7% (14 of 201) of arteries contralateral to symptoms (P < .05). Male sex (P < .05) and increasing age (P < .05) were associated with MR-depicted IPH after controlling for risk factors and medications. CONCLUSION: Complicated carotid atheroma can be found among symptomatic patients with low-grade (≤50%) stenosis, and this is associated with male sex and increasing age. MR-depicted IPH may be useful to stratify risk for patients with low-grade carotid stenosis.

A comparison of the systemic toxicity of lidocaine versus its quaternary derivative QX-314 in mice.

PURPOSE: We recently showed that the quaternary lidocaine derivative, QX-314, produces long-lasting local anesthesia with a slow onset in animal models in vivo. As quaternary agents do not rapidly penetrate biological membranes or the blood-brain barrier, QX-314 may represent a local anesthetic with decreased systemic toxicity compared with conventional tertiary aminoamines. To test this hypothesis, we conducted an in vivo animal study in mice to compare QX-314 with lidocaine in terms of its relative central nervous system (CNS) and cardiac toxicity. METHODS: With approval from the institutional Animal Care Committee, we used the "up-and-down" method to determine the relative potencies (ED(50)) of lidocaine and QX-314 for CNS and cardiac toxicity in adult CD-1 mice (weight, 20 to 35 g). The animals were administered either intravenous lidocaine or QX-314 (dose range, 7.5 to 30 mg·kg(-1)) and were observed for signs of CNS toxicity (convulsions, ataxia, loss of righting reflex, and/or death). We also observed animals for electrocardiographic evidence of toxic effects on cardiac automaticity, conductivity, and rhythmicity. RESULTS: The ED(50) of lidocaine for CNS toxicity as determined by the "up-and-down" method was 19.5 mg·kg(-1) (95% confidence interval [CI], 17.7 to 21.3 mg·kg(-1); n = 6) compared with 10.7 mg·kg(-1) for QX-314 (95% CI, 9.1 to 12.3 mg·kg(-1); n = 6) (potency ratio, 1.8). Similarly, the ED(50) of lidocaine for electrocardiographic evidence of cardiac toxicity was significantly higher than that of QX-314 (ED(50) of lidocaine, 21.2 mg·kg(-1); 95% CI, 19.0 to 23.4 mg·kg(-1); n = 6 vs ED(50) of QX-314, 10.6 mg·kg(-1); 95% CI, 8.4 to 12.8 mg·kg(-1); n = 6) (potency ratio, 2.0). CONCLUSIONS: In this in vivo animal study, the relative potencies of QX-314 for systemic CNS and cardiac toxicity were significantly higher than those of lidocaine. These data do not support the hypothesis that QX-314 is a safer local anesthetic compared with lidocaine in terms of systemic toxicity. Whereas our results do not exclude the possibility that QX-314 may represent a clinically useful agent to produce long-lasting local anesthesia and nociceptive blockade after a single shot in humans, its systemic toxicity relative to conventional tertiary aminoamide local anesthetics and the underlying mechanisms warrant further study.

Lumbar intrathecal administration of the quaternary lidocaine derivative, QX-314, produces irritation and death in mice.

BACKGROUND: We recently found that peripheral administration of the quaternary lidocaine derivative, QX-314, produces long-lasting sensory and motor blockade in animals. The goal of this study was to test whether intrathecal QX-314 has similar properties. METHODS: We conducted a randomized, double-controlled, blinded study with female CD-1 mice. Animals in the treatment group received lumbar intrathecal QX-314 (0.5-10 mM; volume, 2 microl; each concentration, n = 6). Normal saline and lidocaine (70 mM) served as negative and positive controls (each group, n = 12), respectively. Animals were tested for up to 3 h for lumbosacral neural blockade and observed for adverse effects. RESULTS: No animal injected with saline and 11 of 12 (92%) animals injected with lidocaine displayed reversible lumbosacral motor blockade (P < 0.001). QX-314 (5 mM) produced motor blockade in four of the six (67%) and sensory blockade in five of the six animals (83%; P < 0.05 vs. saline). However, six of the six mice (100%) at 5 mM QX-314 and five of the six (83%) at 10 mM exhibited marked irritation; one of the six animals at 5 mM (17%) and two of the six at 10 mM (33%) died. We observed no neural blockade without adverse effects in any animal injected with QX-314. All animals injected with saline and 11 of the 12 (92%) animals injected with lidocaine demonstrated normal behavior. CONCLUSION: Lumbar intrathecal QX-314 concentration-dependently produced irritation and death in mice, at lower concentrations than those associated with robust motor blockade. Although QX-314 did produce long-lasting neural blockade, these findings indicate that QX-314 is unlikely to be a suitable candidate for spinal anesthesia in humans.